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International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.
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International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.
Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.
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Fan H, Wu Y, Yu S, Li X, Wang A, Wang S, Chen W and Lu Y: Critical role of mTOR in regulating aerobic glycolysis in carcinogenesis (review). Int J Oncol. 58:9–19. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Hua H, Kong Q, Zhang H, Wang J, Luo T and Jiang Y: Targeting mTOR for cancer therapy. J Hematol Oncol. 12(71)2019.PubMed/NCBI View Article : Google Scholar | |
|
Zarogoulidis P, Lampaki S, Turner JF, Huang H, Kakolyris S, Syrigos K and Zarogoulidis K: mTOR pathway: A current, up-to-date mini-review (review). Oncol Lett. 8:2367–2370. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Lien EC, Lyssiotis CA and Cantley LC: Metabolic reprogramming by the PI3K-Akt-mTOR pathway in cancer. Recent Results Cancer Res. 207:39–72. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Mossmann D, Park S and Hall MN: mTOR signaling and cellular metabolism are mutual determinants in cancer. Nat Rev Cancer. 18:744–757. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Ramanathan A and Schreiber SL: Direct control of mitochondrial function by mTOR. Proc Natl Acad Sci USA. 106:22229–22232. 2009.PubMed/NCBI View Article : Google Scholar | |
|
Warburg O: On the origin of cancer cells. Science. 123:309–314. 1956.PubMed/NCBI View Article : Google Scholar | |
|
Wang N, Wang B, Maswikiti EP, Yu Y, Song K, Ma C, Han X, Ma H, Deng X, Yu R and Chen H: AMPK-a key factor in crosstalk between tumor cell energy metabolism and immune microenvironment? Cell Death Discov. 10(237)2024.PubMed/NCBI View Article : Google Scholar | |
|
Torres Acosta MA, Gurkan JK, Liu Q, Mambetsariev N, Reyes Flores C, Helmin KA, Joudi AM, Morales-Nebreda L, Cheng K, Abdala-Valencia H, et al: AMPK is necessary for Treg functional adaptation to microenvironmental stress during malignancy and viral pneumonia. J Clin Invest. 135(e179572)2025.PubMed/NCBI View Article : Google Scholar | |
|
Marafie SK, Al-Mulla F and Abubaker J: mTOR: Its critical role in metabolic diseases, cancer, and the aging process. Int J Mol Sci. 25(6141)2024.PubMed/NCBI View Article : Google Scholar | |
|
Smiles WJ, Ovens AJ, Kemp BE, Galic S, Petersen J and Oakhill JS: New developments in AMPK and mTORC1 cross-talk. Essays Biochem. 68:321–336. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Keerthana CK, Rayginia TP, Shifana SC, Anto NP, Kalimuthu K, Isakov N and Anto RJ: The role of AMPK in cancer metabolism and its impact on the immunomodulation of the tumor microenvironment. Front Immunol. 14(1114582)2023.PubMed/NCBI View Article : Google Scholar | |
|
Zhang T, Wang X, Alexander PG, Feng P and Zhang J: An analysis of AMPK and ferroptosis in cancer: A potential regulatory axis. Front Biosci (Landmark Ed). 30(36618)2025.PubMed/NCBI View Article : Google Scholar | |
|
Liao H, Wang Y, Zou L, Fan Y, Wang X, Tu X, Zhu Q, Wang J, Liu X and Dong C: Relationship of mTORC1 and ferroptosis in tumors. Discov Oncol. 15(107)2024.PubMed/NCBI View Article : Google Scholar | |
|
Sun Z, Liu L, Liang H and Zhang L: Nicotinamide mononucleotide induces autophagy and ferroptosis via AMPK/mTOR pathway in hepatocellular carcinoma. Mol Carcinog. 63:577–588. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Wang X, Tan X, Zhang J, Wu J and Shi H: The emerging roles of MAPK-AMPK in ferroptosis regulatory network. Cell Commun Signal. 21(200)2023.PubMed/NCBI View Article : Google Scholar | |
|
Lee H, Zandkarimi F, Zhang Y, Meena JK, Kim J, Zhuang L, Tyagi S, Ma L, Westbrook TF, Steinberg GR, et al: Energy-stress-mediated AMPK activation inhibits ferroptosis. Nat Cell Biol. 22:225–234. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Sun Q, Zhen P, Li D, Liu X, Ding X and Liu H: Amentoflavone promotes ferroptosis by regulating reactive oxygen species (ROS)/5'AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) to inhibit the malignant progression of endometrial carcinoma cells. Bioengineered. 13:13269–13279. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Chen W, Zhao H and Li Y: Mitochondrial dynamics in health and disease: Mechanisms and potential targets. Signal Transduct Target Ther. 8(333)2023.PubMed/NCBI View Article : Google Scholar | |
|
Crosas-Molist E, Graziani V, Maiques O, Pandya P, Monger J, Samain R, George SL, Malik S, Salise J, Morales V, et al: AMPK is a mechano-metabolic sensor linking cell adhesion and mitochondrial dynamics to Myosin-dependent cell migration. Nat Commun. 14(2740)2023.PubMed/NCBI View Article : Google Scholar | |
|
Liu Q, Zhang L, Zou Y, Tao Y, Wang B, Li B, Liu R, Wang B, Ding L, Cui Q, et al: Modulating p-AMPK/mTOR pathway of mitochondrial dysfunction caused by MTERF1 abnormal expression in colorectal cancer cells. Int J Mol Sci. 23(12354)2022.PubMed/NCBI View Article : Google Scholar | |
|
Liu A, Lu X, Song Y, Pei J and Wei R: ACK1 condensates promote STAT5 signaling in lung squamous cell carcinoma. Cancer Cell Int. 25(237)2025.PubMed/NCBI View Article : Google Scholar | |
|
Mehta S and Zhang J: Liquid-liquid phase separation drives cellular function and dysfunction in cancer. Nat Rev Cancer. 22:239–252. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Peng Q, Tan S, Xia L, Wu N, Oyang L, Tang Y, Su M, Luo X, Wang Y, Sheng X, et al: Phase separation in cancer: From the impacts and mechanisms to treatment potentials. Int J Biol Sci. 18:5103–5122. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Maqsood Q, Sumrin A, Saleem MZ, Perveen R, Hussain N, Mahnoor M, Akhtar MW, Wajid A and Ameen E: An insight into cancer from biomolecular condensates. Cancer Screen Prev. 2:177–190. 2023. | |
|
Li Y, Feng Y, Geng S, Xu F and Guo H: The role of liquid-liquid phase separation in defining cancer EMT. Life Sci. 353(122931)2024.PubMed/NCBI View Article : Google Scholar | |
|
Vander Heiden MG, Cantley LC and Thompson CB: Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science. 324:1029–1033. 2009.PubMed/NCBI View Article : Google Scholar | |
|
Warburg O and Minami S: Versuche an Überlebendem carcinom-gewebe. Klin Wochenschr. 2:776–777. 1923. | |
|
Lunt SY and Vander Heiden MG: Aerobic glycolysis: Meeting the metabolic requirements of cell proliferation. Annu Rev Cell Dev Biol. 27:441–464. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Koppenol WH, Bounds PL and Dang CV: Otto Warburg's contributions to current concepts of cancer metabolism. Nat Rev Cancer. 11:325–337. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Tochigi T, Shuto K, Kono T, Ohira G, Tohma T, Gunji H, Hayano K, Narushima K, Fujishiro T, Hanaoka T, et al: Heterogeneity of glucose metabolism in esophageal cancer measured by fractal analysis of fluorodeoxyglucose positron emission tomography image: Correlation between metabolic heterogeneity and survival. Dig Surg. 34:186–191. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Larson SM: Positron emission tomography-based molecular imaging in human cancer: Exploring the link between hypoxia and accelerated glucose metabolism. Clin Cancer Res. 10:2203–2204. 2004.PubMed/NCBI View Article : Google Scholar | |
|
DeBerardinis RJ and Chandel NS: Fundamentals of cancer metabolism. Sci Adv. 2(e1600200)2016.PubMed/NCBI View Article : Google Scholar | |
|
Ward PS and Thompson CB: Metabolic reprogramming: A cancer hallmark even Warburg did not anticipate. Cancer Cell. 21:297–308. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Hsu PP and Sabatini DM: Cancer cell metabolism: Warburg and beyond. Cell. 134:703–707. 2008.PubMed/NCBI View Article : Google Scholar | |
|
Li ZY and Zhang HF: Reprogramming of glucose, fatty acid and amino acid metabolism for cancer progression. Cell Mol Life Sci. 73:377–392. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Kim SY: Cancer energy metabolism: Shutting power off cancer factory. Biomol Ther (Seoul). 26:39–44. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Corbet C and Feron O: Cancer cell metabolism and mitochondria: Nutrient plasticity for TCA cycle fueling. Biochim Biophys Acta Rev Cancer. 1868:7–15. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Weinberg F and Chandel NS: Mitochondrial metabolism and cancer. Ann NY Acad Sci. 1177:66–73. 2009.PubMed/NCBI View Article : Google Scholar | |
|
Zhao L, Mao Y, Zhao Y, Cao Y and Chen X: Role of multifaceted regulators in cancer glucose metabolism and their clinical significance. Oncotarget. 7:31572–31585. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Finley LWS: What is cancer metabolism? Cell. 186:1670–1688. 2023.PubMed/NCBI View Article : Google Scholar | |
|
Stine ZE, Schug ZT, Salvino JM and Dang CV: Targeting cancer metabolism in the era of precision oncology. Nat Rev Drug Discov. 21:141–162. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Vander Heiden MG, Locasale JW, Swanson KD, Sharfi H, Heffron GJ, Amador-Noguez D, Christofk HR, Wagner G, Rabinowitz JD, Asara JM and Cantley LC: Evidence for an alternative glycolytic pathway in rapidly proliferating cells. Science. 329:1492–1499. 2010.PubMed/NCBI View Article : Google Scholar | |
|
Kalyanaraman B, Cheng G, Hardy M, Ouari O, Lopez M, Joseph J, Zielonka J and Dwinell MB: A review of the basics of mitochondrial bioenergetics, metabolism, and related signaling pathways in cancer cells: Therapeutic targeting of tumor mitochondria with lipophilic cationic compounds. Redox Biol. 14:316–327. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Stepien M, Duarte-Salles T, Fedirko V, Floegel A, Barupal DK, Rinaldi S, Achaintre D, Assi N, Tjønneland A, Overvad K, et al: Alteration of amino acid and biogenic amine metabolism in hepatobiliary cancers: Findings from a prospective cohort study. Int J Cancer. 138:348–360. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Frezza C: Cancer metabolism: Addicted to serine. Nat Chem Biol. 12:389–390. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Gordan JD, Thompson CB and Simon MC: HIF and c-Myc: Sibling rivals for control of cancer cell metabolism and proliferation. Cancer Cell. 12:108–113. 2007.PubMed/NCBI View Article : Google Scholar | |
|
West MJ, Stoneley M and Willis AE: Translational induction of the c-myc oncogene via activation of the FRAP/TOR signalling pathway. Oncogene. 17:769–780. 1998.PubMed/NCBI View Article : Google Scholar | |
|
Kalkat M, De Melo J, Hickman KA, Lourenco C, Redel C, Resetca D, Tamachi A, Tu WB and Penn LZ: MYC deregulation in primary human cancers. Genes (Basel). 8(151)2017.PubMed/NCBI View Article : Google Scholar | |
|
Goetzman ES and Prochownik EV: The role for Myc in coordinating glycolysis, oxidative phosphorylation, glutaminolysis, and fatty acid metabolism in normal and neoplastic tissues. Front Endocrinol (Lausanne). 9(129)2018.PubMed/NCBI View Article : Google Scholar | |
|
Pourdehnad M, Truitt ML, Siddiqi IN, Ducker GS, Shokat KM and Ruggero D: Myc and mTOR converge on a common node in protein synthesis control that confers synthetic lethality in Myc-driven cancers. Proc Natl Acad Sci USA. 110:11988–11993. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Sukumaran A, Choi K and Dasgupta B: Insight on transcriptional regulation of the energy sensing AMPK and biosynthetic mTOR pathway genes. Front Cell Dev Biol. 8(671)2020.PubMed/NCBI View Article : Google Scholar | |
|
Khan MW, Biswas D, Ghosh M, Mandloi S, Chakrabarti S and Chakrabarti P: mTORC2 controls cancer cell survival by modulating gluconeogenesis. Cell Death Discov. 1(15016)2015.PubMed/NCBI View Article : Google Scholar | |
|
Sun Q, Chen X, Ma J, Peng H, Wang F, Zha X, Wang Y, Jing Y, Yang H, Chen R, et al: Mammalian target of rapamycin up-regulation of pyruvate kinase isoenzyme type M2 is critical for aerobic glycolysis and tumor growth. Proc Natl Acad Sci USA. 108:4129–4134. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Wei H, Dong C and Shen Z: Kallikrein-related peptidase (KLK10) cessation blunts colorectal cancer cell growth and glucose metabolism by regulating the PI3K/Akt/mTOR pathway. Neoplasma. 67:889–897. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Iqbal MA, Siddiqui FA, Gupta V, Chattopadhyay S, Gopinath P, Kumar B, Manvati S, Chaman N and Bamezai RN: Insulin enhances metabolic capacities of cancer cells by dual regulation of glycolytic enzyme pyruvate kinase M2. Mol Cancer. 12(72)2013.PubMed/NCBI View Article : Google Scholar | |
|
Buller CL, Loberg RD, Fan MH, Zhu Q, Park JL, Vesely E, Inoki K, Guan KL and Brosius FC III: A GSK-3/TSC2/mTOR pathway regulates glucose uptake and GLUT1 glucose transporter expression. Am J Physiol Cell Physiol. 295:C836–C843. 2008.PubMed/NCBI View Article : Google Scholar | |
|
Shi LZ, Wang R, Huang G, Vogel P, Neale G, Green DR and Chi H: HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J Exp Med. 208:1367–1376. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Siska PJ, van der Windt GJW, Kishton RJ, Cohen S, Eisner W, MacIver NJ, Kater AP, Weinberg JB and Rathmell JC: Suppression of Glut1 and glucose metabolism by decreased Akt/mTORC1 signaling drives T cell impairment in B cell leukemia. J Immunol. 197:2532–2540. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Feng Y and Wu L: mTOR up-regulation of PFKFB3 is essential for acute myeloid leukemia cell survival. Biochem Biophys Res Commun. 483:897–903. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Finlay DK, Rosenzweig E, Sinclair LV, Feijoo-Carnero C, Hukelmann JL, Rolf J, Panteleyev AA, Okkenhaug K and Cantrell DA: PDK1 regulation of mTOR and hypoxia-inducible factor 1 integrate metabolism and migration of CD8+ T cells. J Exp Med. 209:2441–2453. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Chen X, Zhu Y, Wang Z, Zhu H, Pan Q, Su S, Dong Y, Li L, Zhang H, Wu L, et al: mTORC1 alters the expression of glycolytic genes by regulating KPNA2 abundances. J Proteomics. 136:13–24. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Li Y, He ZC, Liu Q, Zhou K, Shi Y, Yao XH, Zhang X, Kung HF, Ping YF and Bian XW: Large intergenic non-coding RNA-RoR inhibits aerobic glycolysis of glioblastoma cells via Akt pathway. J Cancer. 9:880–889. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Holloway RW and Marignani PA: Targeting mTOR and glycolysis in HER2-positive breast cancer. Cancers (Basel). 13(2922)2021.PubMed/NCBI View Article : Google Scholar | |
|
Dibble CC and Manning BD: Signal integration by mTORC1 coordinates nutrient input with biosynthetic output. Nat Cell Biol. 15:555–564. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Kullmann L and Krahn MP: Controlling the master-upstream regulation of the tumor suppressor LKB1. Oncogene. 37:3045–3057. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Zhang J, Pavlova NN and Thompson CB: Cancer cell metabolism: The essential role of the nonessential amino acid, glutamine. EMBO J. 36:1302–1315. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Altman BJ, Stine ZE and Dang CV: From Krebs to clinic: Glutamine metabolism to cancer therapy. Nat Rev Cancer. 16:619–634. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Choi YK and Park KG: Targeting glutamine metabolism for cancer treatment. Biomol Ther (Seoul). 26:19–28. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Masui K, Tanaka K, Akhavan D, Babic I, Gini B, Matsutani T, Iwanami A, Liu F, Villa GR, Gu Y, et al: mTOR complex 2 controls glycolytic metabolism in glioblastoma through FoxO acetylation and upregulation of c-Myc. Cell Metab. 18:726–739. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Prieto J, García-Cañaveras JC, León M, Sendra R, Ponsoda X, Izpisúa Belmonte JC, Lahoz A and Torres J: c-MYC triggers lipid remodelling during early somatic cell reprogramming to pluripotency. Stem Cell Rev Rep. 17:2245–2261. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Khan MW, Layden BT and Chakrabarti P: Inhibition of mTOR complexes protects cancer cells from glutamine starvation induced cell death by restoring Akt stability. Biochim Biophys Acta Mol Basis Dis. 1864:2040–2052. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Csibi A, Lee G, Yoon SO, Tong H, Ilter D, Elia I, Fendt SM, Roberts TM and Blenis J: The mTORC1/S6K1 pathway regulates glutamine metabolism through the eIF4B-dependent control of c-Myc translation. Curr Biol. 24:2274–2280. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Shaw E, Talwadekar M, Rashida Z, Mohan N, Acharya A, Khatri S, Laxman S and Kolthur-Seetharam U: Anabolic SIRT4 exerts retrograde control over TORC1 signaling by glutamine sparing in the mitochondria. Mol Cell Biol. 40:e00212–19. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Wang D, He J, Huang B, Liu S, Zhu H and Xu T: Emerging role of the Hippo pathway in autophagy. Cell Death Dis. 11(880)2020.PubMed/NCBI View Article : Google Scholar | |
|
Trejo-Solís C, Serrano-García N, Castillo-Rodríguez RA, Robledo-Cadena DX, Jimenez-Farfan D, Marín-Hernández Á, Silva-Adaya D, Rodríguez-Pérez CE and Gallardo-Pérez JC: Metabolic dysregulation of tricarboxylic acid cycle and oxidative phosphorylation in glioblastoma. Rev Neurosci. 35:813–838. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Morita M, Gravel SP, Chénard V, Sikström K, Zheng L, Alain T, Gandin V, Avizonis D, Arguello M, Zakaria C, et al: mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translational regulation. Cell Metab. 18:698–711. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Wise DR, DeBerardinis RJ, Mancuso A, Sayed N, Zhang XY, Pfeiffer HK, Nissim I, Daikhin E, Yudkoff M, McMahon SB and Thompson CB: Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc Natl Acad Sci USA. 105:18782–18787. 2008.PubMed/NCBI View Article : Google Scholar | |
|
Byun JK, Choi YK, Kim JH, Jeong JY, Jeon HJ, Kim MK, Hwang I, Lee SY, Lee YM, Lee IK and Park KG: A positive feedback loop between Sestrin2 and mTORC2 is required for the survival of glutamine-depleted lung cancer cells. Cell Rep. 20:586–599. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Durán RV, Oppliger W, Robitaille AM, Heiserich L, Skendaj R, Gottlieb E and Hall MN: Glutaminolysis activates Rag-mTORC1 signaling. Mol Cell. 47:349–358. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Chiu M, Tardito S, Barilli A, Bianchi MG, Dall'Asta V and Bussolati O: Glutamine stimulates mTORC1 independent of the cell content of essential amino acids. Amino Acids. 43:2561–2567. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Bodineau C, Tomé M, Courtois S, Costa ASH, Sciacovelli M, Rousseau B, Richard E, Vacher P, Parejo-Pérez C, Bessede E, et al: Two parallel pathways connect glutamine metabolism and mTORC1 activity to regulate glutamoptosis. Nat Commun. 12(4814)2021.PubMed/NCBI View Article : Google Scholar | |
|
Dennis MD, Jefferson LS and Kimball SR: Role of p70S6K1-mediated phosphorylation of eIF4B and PDCD4 proteins in the regulation of protein synthesis. J Biol Chem. 287:42890–42899. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Dalle Pezze P, Ruf S, Sonntag AG, Langelaar-Makkinje M, Hall P, Heberle AM, Razquin Navas P, van Eunen K, Tölle RC, Schwarz JJ, et al: A systems study reveals concurrent activation of AMPK and mTOR by amino acids. Nat Commun. 7(13254)2016.PubMed/NCBI View Article : Google Scholar | |
|
Nicklin P, Bergman P, Zhang B, Triantafellow E, Wang H, Nyfeler B, Yang H, Hild M, Kung C, Wilson C, et al: Bidirectional transport of amino acids regulates mTOR and autophagy. Cell. 136:521–534. 2009.PubMed/NCBI View Article : Google Scholar | |
|
Selwan EM and Edinger AL: Branched chain amino acid metabolism and cancer: The importance of keeping things in context. Transl Cancer Res. 6 (Suppl 3):S578–S584. 2017.PubMed/NCBI View Article : Google Scholar | |
|
McCracken AN and Edinger AL: Nutrient transporters: The Achilles' heel of anabolism. Trends Endocrin Met. 24:200–208. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Kawasome H, Papst P, Webb S, Keller GM, Johnson GL, Gelfand EW and Terada N: Targeted disruption of p70(s6k) defines its role in protein synthesis and rapamycin sensitivity. Proc Natl Acad Sci USA. 95:5033–5038. 1998.PubMed/NCBI View Article : Google Scholar | |
|
Martineau Y, Wang X, Alain T, Petroulakis E, Shahbazian D, Fabre B, Bousquet-Dubouch MP, Monsarrat B, Pyronnet S and Sonenberg N: Control of Paip1-eukaryotic translation initiation factor 3 interaction by amino acids through S6 kinase. Mol Cell Biol. 34:1046–1053. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Iadevaia V, Liu R and Proud CG: mTORC1 signaling controls multiple steps in ribosome biogenesis. Semin Cell Dev Biol. 36:113–120. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Abetov DA, Kiyan VS, Zhylkibayev AA, Sarbassova DA, Alybayev SD, Spooner E, Song MS, Bersimbaev RI and Sarbassov DD: Formation of mammalian preribosomes proceeds from intermediate to composed state during ribosome maturation. J Biol Chem. 294:10746–10757. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Gentilella A, Kozma SC and Thomas G: A liaison between mTOR signaling, ribosome biogenesis and cancer. Biochim Biophys Acta. 1849:812–820. 2015.PubMed/NCBI View Article : Google Scholar | |
|
He J, Yang Y, Zhang J, Chen J, Wei X, He J and Luo L: Ribosome biogenesis protein Urb1 acts downstream of mTOR complex 1 to modulate digestive organ development in zebrafish. J Genet Genomics. 44:567–576. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Rad E, Murray JT and Tee AR: Oncogenic signalling through mechanistic target of rapamycin (mTOR): A driver of metabolic transformation and cancer progression. Cancers (Basel). 10(5)2018.PubMed/NCBI View Article : Google Scholar | |
|
Qin L, Cheng X, Wang S, Gong G, Su H, Huang H, Chen T, Damdinjav D, Dorjsuren B, Li Z, et al: Discovery of novel aminobutanoic acid-based ASCT2 inhibitors for the treatment of non-small-cell lung cancer. J Med Chem. 67:988–1007. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Leibowitz BJ, Zhao G, Xia W, Wang Y, Ruan H, Zhang L and Yu J: mTOR inhibition suppresses Myc-driven polyposis by inducing immunogenic cell death. Oncogene. 42:2007–2016. 2023.PubMed/NCBI View Article : Google Scholar | |
|
Elkon R, Loayza-Puch F, Korkmaz G, Lopes R, van Breugel PC, Bleijerveld OB, Altelaar AF, Wolf E, Lorenzin F, Eilers M and Agami R: Myc coordinates transcription and translation to enhance transformation and suppress invasiveness. EMBO Rep. 16:1723–1736. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Peng T, Golub TR and Sabatini DM: The immunosuppressant rapamycin mimics a starvation-like signal distinct from amino acid and glucose deprivation. Mol Cell Biol. 22:5575–5584. 2002.PubMed/NCBI View Article : Google Scholar | |
|
Rosario FJ, Kanai Y, Powell TL and Jansson T: Mammalian target of rapamycin signalling modulates amino acid uptake by regulating transporter cell surface abundance in primary human trophoblast cells. J Physiol. 591:609–625. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Rosario FJ, Dimasuay KG, Kanai Y, Powell TL and Jansson T: Regulation of amino acid transporter trafficking by mTORC1 in primary human trophoblast cells is mediated by the ubiquitin ligase Nedd4-2. Clin Sci (Lond). 130:499–512. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Park Y, Reyna-Neyra A, Philippe L and Thoreen CC: mTORC1 balances cellular amino acid supply with demand for protein synthesis through post-transcriptional control of ATF4. Cell Rep. 19:1083–1090. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Gu Y, Albuquerque CP, Braas D, Zhang W, Villa GR, Bi J, Ikegami S, Masui K, Gini B, Yang H, et al: mTORC2 regulates amino acid metabolism in cancer by phosphorylation of the cystine-glutamate antiporter xCT. Mol Cell. 67:128–138.e7. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Toda K, Kawada K, Iwamoto M, Inamoto S, Sasazuki T, Shirasawa S, Hasegawa S and Sakai Y: Metabolic alterations caused by KRAS mutations in colorectal cancer contribute to cell adaptation to glutamine depletion by upregulation of asparagine synthetase. Neoplasia. 18:654–665. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Pupo E, Avanzato D, Middonti E, Bussolino F and Lanzetti L: KRAS-driven metabolic rewiring reveals novel actionable targets in cancer. Front Oncol. 9(848)2019.PubMed/NCBI View Article : Google Scholar | |
|
Gwinn DM, Lee AG, Briones-Martin-Del-Campo M, Conn CS, Simpson DR, Scott AI, Le A, Cowan TM, Ruggero D and Sweet-Cordero EA: Oncogenic KRAS regulates amino acid homeostasis and asparagine biosynthesis via ATF4 and alters sensitivity to L-asparaginase. Cancer Cell. 33:91–107.e6. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Long Y, Tsai WB, Wangpaichitr M, Tsukamoto T, Savaraj N, Feun LG and Kuo MT: Arginine deiminase resistance in melanoma cells is associated with metabolic reprogramming, glucose dependence, and glutamine addiction. Mol Cancer Ther. 12:2581–2590. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Selvarajah B, Azuelos I, Platé M, Guillotin D, Forty EJ, Contento G, Woodcock HV, Redding M, Taylor A, Brunori G, et al: mTORC1 amplifies the ATF4-dependent de novo serine-glycine pathway to supply glycine during TGF-β1-induced collagen biosynthesis. Sci Signal. 12(eaav3048)2019.PubMed/NCBI View Article : Google Scholar | |
|
Kma L and Baruah TJ: The interplay of ROS and the PI3K/Akt pathway in autophagy regulation. Biotechnol Appl Biochem. 69:248–264. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Horton JD, Goldstein JL and Brown MS: SREBPs: Activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest. 109:1125–1131. 2002.PubMed/NCBI View Article : Google Scholar | |
|
Randle PJ: Regulatory interactions between lipids and carbohydrates: The glucose fatty acid cycle after 35 years. Diabetes Metab Rev. 14:263–283. 1998.PubMed/NCBI View Article : Google Scholar | |
|
Chen Y and Li P: Fatty acid metabolism and cancer development. Sci Bull. 61:1473–1479. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Alasadi A, Humaish HH and Al-hraishawi H: Evaluation the predictors of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus (T2DM) patients. Syst Rev Pharm. 11:421–430. 2020. | |
|
Mullen AR, Wheaton WW, Jin ES, Chen PH, Sullivan LB, Cheng T, Yang Y, Linehan WM, Chandel NS and DeBerardinis RJ: Reductive carboxylation supports growth in tumour cells with defective mitochondria. Nature. 481:385–388. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Metallo CM, Gameiro PA, Bell EL, Mattaini KR, Yang J, Hiller K, Jewell CM, Johnson ZR, Irvine DJ, Guarente L, et al: Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature. 481:380–384. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Wise DR, Ward PS, Shay JE, Cross JR, Gruber JJ, Sachdeva UM, Platt JM, DeMatteo RG, Simon MC and Thompson CB: Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of α-ketoglutarate to citrate to support cell growth and viability. Proc Natl Acad Sci USA. 108:19611–19616. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Schug ZT, Peck B, Jones DT, Zhang Q, Grosskurth S, Alam IS, Goodwin LM, Smethurst E, Mason S, Blyth K, et al: Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress. Cancer Cell. 27:57–71. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Green CR, Wallace M, Divakaruni AS, Phillips SA, Murphy AN, Ciaraldi TP and Metallo CM: Branched-chain amino acid catabolism fuels adipocyte differentiation and lipogenesis. Nat Chem Biol. 12:15–21. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Eberlé D, Hegarty B, Bossard P, Ferré P and Foufelle F: SREBP transcription factors: master regulators of lipid homeostasis. Biochimie. 86:839–848. 2004.PubMed/NCBI View Article : Google Scholar | |
|
Nakamura MT, Cheon Y, Li Y and Nara TY: Mechanisms of regulation of gene expression by fatty acids. Lipids. 39:1077–1083. 2004.PubMed/NCBI View Article : Google Scholar | |
|
Pégorier JP, Le May C and Girard J: Control of gene expression by fatty acids. J Nutr. 134:2444S–2449S. 2004.PubMed/NCBI View Article : Google Scholar | |
|
Düvel K, Yecies JL, Menon S, Raman P, Lipovsky AI, Souza AL, Triantafellow E, Ma Q, Gorski R, Cleaver S, et al: Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Mol Cell. 39:171–183. 2010.PubMed/NCBI View Article : Google Scholar | |
|
DeBerardinis RJ, Lum JJ and Thompson CB: Phosphatidylinositol 3-kinase-dependent modulation of carnitine palmitoyltransferase 1A expression regulates lipid metabolism during hematopoietic cell growth. J Biol Chem. 281:37372–37380. 2006.PubMed/NCBI View Article : Google Scholar | |
|
Hao YJ, Samuels Y, Li QL, Krokowski D, Brunengraber H, Hatzoglou M, Zhang GF, Vogelstein B and Wang Z: Abstract 1125: Oncogenic PIK3CA mutations reprogram glutamine metabolism in colorectal cancers. Cancer Res. 75 (15 Suppl)(S1125)2015.PubMed/NCBI View Article : Google Scholar | |
|
Liu C, Zhou X, Pan Y, Liu Y and Zhang Y: Pyruvate carboxylase promotes thyroid cancer aggressiveness through fatty acid synthesis. BMC Cancer. 21(722)2021.PubMed/NCBI View Article : Google Scholar | |
|
Schiliro C and Firestein BL: Mechanisms of metabolic reprogramming in cancer cells supporting enhanced growth and proliferation. Cells. 10(1056)2021.PubMed/NCBI View Article : Google Scholar | |
|
Andrade-Vieira R, Han JH and Marignani PA: Omega-3 polyunsaturated fatty acid promotes the inhibition of glycolytic enzymes and mTOR signaling by regulating the tumor suppressor LKB1. Cancer Biol Ther. 14:1050–1058. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Kuma A, Hatano M, Matsui M, Yamamoto A, Nakaya H, Yoshimori T, Ohsumi Y, Tokuhisa T and Mizushima N: The role of autophagy during the early neonatal starvation period. Nature. 432:1032–1036. 2004.PubMed/NCBI View Article : Google Scholar | |
|
Alasadi AH, Guo J, Tao H and Jin S: Preventing and treating hepatic metastatic colon and pancreatic cancers by targeting cell metabolism. Cancer Res. 76 (14 Suppl)(S45)2016. | |
|
Aird KM and Zhang R: Nucleotide metabolism, oncogene-induced senescence and cancer. Cancer Lett. 356:204–210. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Cantor JR and Sabatini DM: Cancer cell metabolism: One hallmark, many faces. Cancer Discov. 2:881–898. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Vander Heiden MG: Targeting cancer metabolism: A therapeutic window opens. Nat Rev Drug Discov. 10:671–684. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Ben-Sahra I, Howell JJ, Asara JM and Manning BD: Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1. Science. 339:1323–1328. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Robitaille AM, Christen S, Shimobayashi M, Cornu M, Fava LL, Moes S, Prescianotto-Baschong C, Sauer U, Jenoe P and Hall MN: Quantitative phosphoproteomics reveal mTORC1 activates de novo pyrimidine synthesis. Science. 339:1320–1323. 2013.PubMed/NCBI View Article : Google Scholar | |
|
He L, Wei X, Ma X, Yin X, Song M, Donninger H, Yaddanapudi K, McClain CJ and Zhang X: Simultaneous quantification of nucleosides and nucleotides from biological samples. J Am Soc Mass Spectrom. 30:987–1000. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Qian X, Li X, Tan L, Lee JH, Xia Y, Cai Q, Zheng Y, Wang H, Lorenzi PL and Lu Z: Conversion of PRPS hexamer to monomer by AMPK-mediated phosphorylation inhibits nucleotide synthesis in response to energy stress. Cancer Discov. 8:94–107. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Yecies JL, Zhang HH, Menon S, Liu S, Yecies D, Lipovsky AI, Gorgun C, Kwiatkowski DJ, Hotamisligil GS, Lee CH and Manning BD: Akt stimulates hepatic SREBP1c and lipogenesis through parallel mTORC1-dependent and independent pathways. Cell Metab. 14:21–32. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Chen J, Yang S, Li Y, Ziwen X, Zhang P, Song Q, Yao Y and Pei H: De novo nucleotide biosynthetic pathway and cancer. Genes Dis. 10:2331–2338. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Qian J, Chen Y, Meng T, Ma L, Meng L, Wang X, Yu T, Zask A, Shen J and Yu K: Molecular regulation of apoptotic machinery and lipid metabolism by mTORC1/mTORC2 dual inhibitors in preclinical models of HER2+/PIK3CAmut breast cancer. Oncotarget. 7:67071–67086. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Evert M, Calvisi DF, Evert K, De Murtas V, Gasparetti G, Mattu S, Destefanis G, Ladu S, Zimmermann A, Delogu S, et al: V-AKT murine thymoma viral oncogene homolog/mammalian target of rapamycin activation induces a module of metabolic changes contributing to growth in insulin-induced hepatocarcinogenesis. Hepatology. 55:1473–1484. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Cheng J, Huang Y, Zhang X, Yu Y, Wu S, Jiao J, Tran L, Zhang W, Liu R, Zhang L, et al: TRIM21 and PHLDA3 negatively regulate the crosstalk between the PI3K/AKT pathway and PPP metabolism. Nat Commun. 11(1880)2020.PubMed/NCBI View Article : Google Scholar | |
|
Saha A, Connelly S, Jiang J, Zhuang S, Amador DT, Phan T, Pilz RB and Boss GR: Akt phosphorylation and regulation of transketolase is a nodal point for amino acid control of purine synthesis. Mol Cell. 55:264–276. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Wang W and Guan KL: AMP-activated protein kinase and cancer. Acta Physiol (Oxf). 196:55–63. 2009.PubMed/NCBI View Article : Google Scholar | |
|
Cantó C and Auwerx J: Calorie restriction: Is AMPK a key sensor and effector? Physiology (Bethesda). 26:214–224. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Klaus S, Keipert S, Rossmeisl M and Kopecky J: Augmenting energy expenditure by mitochondrial uncoupling: A role of AMP-activated protein kinase. Genes Nutr. 7:369–386. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Fujii N, Aschenbach WG, Musi N, Hirshman MF and Goodyear LJ: Regulation of glucose transport by the AMP-activated protein kinase. Proc Nutr Soc. 63:205–210. 2004.PubMed/NCBI View Article : Google Scholar | |
|
Haurie V, Boucherie H and Sagliocco F: The Snf1 protein kinase controls the induction of genes of the iron uptake pathway at the diauxic shift in Saccharomyces cerevisiae. J Biol Chem. 278:45391–45396. 2003.PubMed/NCBI View Article : Google Scholar | |
|
Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, et al: Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 108:1167–1174. 2001.PubMed/NCBI View Article : Google Scholar | |
|
Hawley SA, Fullerton MD, Ross FA, Schertzer JD, Chevtzoff C, Walker KJ, Peggie MW, Zibrova D, Green KA, Mustard KJ, et al: The ancient drug salicylate directly activates AMP-activated protein kinase. Science. 336:918–922. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Daurio NA, Tuttle SW, Worth AJ, Song EY, Davis JM, Snyder NW, Blair IA and Koumenis C: AMPK activation and metabolic reprogramming by tamoxifen through estrogen receptor-independent mechanisms suggests new uses for this therapeutic modality in cancer treatment. Cancer Res. 76:3295–3306. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Xiao B, Heath R, Saiu P, Leiper FC, Leone P, Jing C, Walker PA, Haire L, Eccleston JF, Davis CT, et al: Structural basis for AMP binding to mammalian AMP-activated protein kinase. Nature. 449:496–500. 2007.PubMed/NCBI View Article : Google Scholar | |
|
Scott JW, Hawley SA, Green KA, Anis M, Stewart G, Scullion GA, Norman DG and Hardie DG: CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations. J Clin Invest. 113:274–284. 2004.PubMed/NCBI View Article : Google Scholar | |
|
Gowans GJ, Hawley SA, Ross FA and Hardie DG: AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation. Cell Metab. 18:556–566. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Hardie DG: Molecular pathways: Is AMPK a friend or a foe in cancer? Clin Cancer Res. 21:3836–3840. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Faubert B, Vincent EE, Griss T, Samborska B, Izreig S, Svensson RU, Mamer OA, Avizonis D, Shackelford DB, Shaw RJ and Jones RG: Loss of the tumor suppressor LKB1 promotes metabolic reprogramming of cancer cells via HIF-1α. Proc Natl Acad Sci USA. 111:2554–2559. 2014.PubMed/NCBI View Article : Google Scholar | |
|
El-Masry OS, Brown BL and Dobson PRM: Effects of activation of AMPK on human breast cancer cell lines with different genetic backgrounds. Oncol Lett. 3:224–228. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Hadad SM, Baker L, Quinlan PR, Robertson KE, Bray SE, Thomson G, Kellock D, Jordan LB, Purdie CA, Hardie DG, et al: Histological evaluation of AMPK signaling in primary breast cancer. BMC Cancer. 9(307)2009.PubMed/NCBI View Article : Google Scholar | |
|
Lee CW, Wong LLY, Tse EYT, Liu HF, Leong VY, Lee JM, Hardie DG, Ng IO and Ching YP: AMPK promotes p53 acetylation via phosphorylation and inactivation of SIRT1 in liver cancer cells. Cancer Res. 72:4394–4404. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Laderoute KR, Calaoagan JM, Chao WR, Dinh D, Denko N, Duellman S, Kalra J, Liu X, Papandreou I, Sambucetti L and Boros LG: 5'-AMP-activated protein kinase (AMPK) supports the growth of aggressive experimental human breast cancer tumors. J Biol Chem. 289:22850–22864. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Zheng L, Yang W, Wu F, Wang C, Yu L, Tang L, Qiu B, Li Y, Guo L, Wu M, et al: Prognostic significance of AMPK activation and therapeutic effects of metformin in hepatocellular carcinoma. Clin Cancer Res. 19:5372–5380. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Faubert B, Boily G, Izreig S, Griss T, Samborska B, Dong Z, Dupuy F, Chambers C, Fuerth BJ, Viollet B, et al: AMPK is a negative regulator of the Warburg effect and suppresses tumor growth in vivo. Cell Metab. 17:113–124. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Sanchez-Cespedes M, Parrella P, Esteller M, Nomoto S, Trink B, Engles JM, Westra WH, Herman JG and Sidransky D: Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung. Cancer Res. 62:3659–3662. 2002.PubMed/NCBI | |
|
Ji H, Ramsey MR, Hayes DN, Fan C, McNamara K, Kozlowski P, Torrice C, Wu MC, Shimamura T, Perera SA, et al: LKB1 modulates lung cancer differentiation and metastasis. Nature. 448:807–810. 2007.PubMed/NCBI View Article : Google Scholar | |
|
Wingo SN, Gallardo TD, Akbay EA, Liang MC, Contreras CM, Boren T, Shimamura T, Miller DS, Sharpless NE, Bardeesy N, et al: Somatic LKB1 mutations promote cervical cancer progression. PLoS One. 4(e5137)2009.PubMed/NCBI View Article : Google Scholar | |
|
Hawley SA, Ross FA, Gowans GJ, Tibarewal P, Leslie NR and Hardie DG: Phosphorylation by Akt within the ST loop of AMPK-α1 down-regulates its activation in tumour cells. Biochem J. 459:275–287. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Horman S, Vertommen D, Heath R, Neumann D, Mouton V, Woods A, Schlattner U, Wallimann T, Carling D, Hue L and Rider MH: Insulin antagonizes ischemia-induced Thr172 phosphorylation of AMP-activated protein kinase alpha-subunits in heart via hierarchical phosphorylation of Ser485/491. J Biol Chem. 281:5335–5340. 2006.PubMed/NCBI View Article : Google Scholar | |
|
Hay N and Sonenberg N: Upstream and downstream of mTOR. Genes Dev. 18:1926–1945. 2004.PubMed/NCBI View Article : Google Scholar | |
|
Zhang Y, Li W, Niu J, Fan Z, Li X and Zhang H: Reprogramming of glucose metabolism in pancreatic cancer: Mechanisms, implications, and therapeutic perspectives. Front Immunol. 16(1586959)2025.PubMed/NCBI View Article : Google Scholar | |
|
Du W, Xu A, Huang Y, Cao J, Zhu H, Yang B, Shao X, He Q and Ying M: The role of autophagy in targeted therapy for acute myeloid leukemia. Autophagy. 17:2665–2679. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Mohanty SS, Warrier S and Rangarajan A: Rethinking AMPK: A reversible switch fortifying cancer cell stress-resilience. Yale J Biol Med. 98:33–52. 2025.PubMed/NCBI View Article : Google Scholar | |
|
Baek SY, Hwang UW, Suk HY and Kim YW: Hemistepsin A inhibits cell proliferation and induces G0/G1-phase arrest, cellular senescence and apoptosis via the AMPK and p53/p21 signals in human hepatocellular carcinoma. Biomolecules. 10(713)2020.PubMed/NCBI View Article : Google Scholar | |
|
Wang EM, Akasaka H, Zhao J, Varadhachary GR, Lee JE, Maitra A, Fleming JB, Hung MC, Wang H and Katz MHG: Expression and clinical significance of protein kinase RNA-like endoplasmic reticulum kinase and phosphorylated eukaryotic initiation factor 2α in pancreatic ductal adenocarcinoma. Pancreas. 48:323–328. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Grenier A, Poulain L, Mondesir J, Jacquel A, Bosc C, Stuani L, Mouche S, Larrue C, Sahal A, Birsen R, et al: AMPK-PERK axis represses oxidative metabolism and enhances apoptotic priming of mitochondria in acute myeloid leukemia. Cell Rep. 38(110197)2022.PubMed/NCBI View Article : Google Scholar | |
|
Wang S, Li H, Yuan M, Fan H and Cai Z: Role of AMPK in autophagy. Front Physiol. 13(1015500)2022.PubMed/NCBI View Article : Google Scholar | |
|
Panina SB, Pei J and Kirienko NV: Mitochondrial metabolism as a target for acute myeloid leukemia treatment. Cancer Metab. 9(17)2021.PubMed/NCBI View Article : Google Scholar | |
|
Liu Y and Ma Z: Leukemia and mitophagy: A novel perspective for understanding oncogenesis and resistance. Ann Hematol. 103:2185–2196. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Li Y, Sun R, Zou J, Ying Y and Luo Z: Dual roles of the AMP-activated protein kinase pathway in angiogenesis. Cells. 8(752)2019.PubMed/NCBI View Article : Google Scholar | |
|
Carling D: AMPK hierarchy: A matter of space and time. Cell Res. 29:425–426. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Uprety B and Abrahamse H: Targeting breast cancer and their stem cell population through AMPK activation: Novel insights. Cells. 11(576)2022.PubMed/NCBI View Article : Google Scholar | |
|
Jhaveri TZ, Woo J, Shang X, Park BH and Gabrielson E: AMP-activated kinase (AMPK) regulates activity of HER2 and EGFR in breast cancer. Oncotarget. 6:14754–14765. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Göbel A, Riffel RM, Hofbauer LC and Rachner TD: The mevalonate pathway in breast cancer biology. Cancer Lett. 542(215761)2022.PubMed/NCBI View Article : Google Scholar | |
|
Amengual-Cladera E, Morla-Barcelo PM, Morán-Costoya A, Sastre-Serra J, Pons DG, Valle A, Roca P and Nadal-Serrano M: Metformin: From diabetes to cancer-unveiling molecular mechanisms and therapeutic strategies. Biology (Basel). 13(302)2024.PubMed/NCBI View Article : Google Scholar | |
|
Pei W, Dai L, Li M, Cao S, Xiao Y, Yang Y, Ma M, Deng M, Mo Y and Liu M: Targeting mitochondrial quality control for the treatment of triple-negative breast cancer: From molecular mechanisms to precision therapy. Biomolecules. 15(970)2025.PubMed/NCBI View Article : Google Scholar | |
|
Lim JS, Kim E, Song JS and Ahn S: Energy-stress-mediated activation of AMPK sensitizes MPS1 kinase inhibition in triple-negative breast cancer. Oncol Rep. 52(101)2024.PubMed/NCBI View Article : Google Scholar | |
|
Mustafa M, Abbas K, Alam M, Ahmad W, Moinuddin Usmani N, Siddiqui SA and Habib S: Molecular pathways and therapeutic targets linked to triple-negative breast cancer (TNBC). Mol Cell Biochem. 479:895–913. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Li C, Syed MU, Nimbalkar A, Shen Y, Vieira MD, Fraser C, Inde Z, Qin X, Ouyang J, Kreuzer J, et al: LKB1 regulates JNK-dependent stress signaling and apoptotic dependency of KRAS-mutant lung cancers. Nat Commun. 16(4112)2025.PubMed/NCBI View Article : Google Scholar | |
|
Huang Q, Ren Y, Yuan P, Huang M, Liu G, Shi Y, Jia G and Chen M: Targeting the AMPK/Nrf2 pathway: A novel therapeutic approach for acute lung injury. J Inflamm Res. 17:4683–4700. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Fatehi Hassanabad A and MacQueen KT: Molecular mechanisms underlining the role of metformin as a therapeutic agent in lung cancer. Cell Oncol (Dordr). 44:1–18. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Bernasconi R, Soodla K, Sirp A, Zovo K, Kuhtinskaja M, Lukk T, Vendelin M and Birkedal R: Higher AMPK activation in mouse oxidative compared with glycolytic muscle does not correlate with LKB1 or CaMKKβ expression. Am J Physiol Endocrinol Metab. 328:E21–E33. 2025.PubMed/NCBI View Article : Google Scholar | |
|
Sumbly V and Landry I: Unraveling the role of STK11/LKB1 in non-small cell lung cancer. Cureus. 14(e21078)2022.PubMed/NCBI View Article : Google Scholar | |
|
Shi Y, Zheng H, Wang T, Zhou S, Zhao S, Li M and Cao B: Targeting KRAS: From metabolic regulation to cancer treatment. Mol Cancer. 24(9)2025.PubMed/NCBI View Article : Google Scholar | |
|
Liu H, Zhou D, Ou Y, Chen S, Long Y, Yuan T, Li Y and Tan Y: Multiple signaling pathways in the frontiers of lung cancer progression. Front Immunol. 16(1593793)2025.PubMed/NCBI View Article : Google Scholar | |
|
Yibcharoenporn C, Muanprasat C, Moonwiriyakit A, Satitsri S and Pathomthongtaweechai N: AMPK in intestinal health and disease: A multifaceted therapeutic target for metabolic and inflammatory disorders. Drug Des Devel Ther. 19:3029–3058. 2025.PubMed/NCBI View Article : Google Scholar | |
|
Li S, Wang Y, Zhang D, Wang H, Cui X, Zhang C and Xin Y: Gliclazide reduces colitis-associated colorectal cancer formation by deceasing colonic inflammation and regulating AMPK-NF-κB signaling pathway. Dig Dis Sci. 69:453–462. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Su G, Wang D, Yang Q, Kong L, Ju X, Yang Q, Zhu Y, Zhang S and Li Y: Cepharanthine suppresses APC-mutant colorectal cancers by down-regulating the expression of β-catenin. Nat Prod Bioprospect. 14(18)2024.PubMed/NCBI View Article : Google Scholar | |
|
Liu JY, Liu JX, Li R, Zhang ZQ, Zhang XH, Xing SJ, Sui BD, Jin F, Ma B and Zheng CX: AMPK, a hub for the microenvironmental regulation of bone homeostasis and diseases. J Cell Physiol. 239(e31393)2024.PubMed/NCBI View Article : Google Scholar | |
|
Fakhri S, Moradi SZ, Moradi SY, Piri S, Shiri Varnamkhasti B, Piri S, Khirehgesh MR and Bishayee A, Casarcia N and Bishayee A: Phytochemicals regulate cancer metabolism through modulation of the AMPK/PGC-1α signaling pathway. BMC Cancer. 24(1079)2024.PubMed/NCBI View Article : Google Scholar | |
|
Cheng D, Zhang M, Zheng Y, Wang M, Gao Y, Wang X, Liu X, Lv W, Zeng X, Belosludtsev KN, et al: α-Ketoglutarate prevents hyperlipidemia-induced fatty liver mitochondrial dysfunction and oxidative stress by activating the AMPK-pgc-1α/Nrf2 pathway. Redox Biol. 74(103230)2024.PubMed/NCBI View Article : Google Scholar | |
|
Naiini MR, Shahouzehi B, Azizi S, Shafiei B and Nazari-Robati M: Trehalose-induced SIRT1/AMPK activation regulates SREBP-1c/PPAR-α to alleviate lipid accumulation in aged liver. Naunyn Schmiedebergs Arch Pharmacol. 397:1061–1070. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Cunha V, Cotrim HP, Rocha R, Carvalho K and Lins-Kusterer L: Metformin in the prevention of hepatocellular carcinoma in diabetic patients: A systematic review. Ann Hepatol. 19:232–237. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Tufail M, Jiang CH and Li N: Altered metabolism in cancer: Insights into energy pathways and therapeutic targets. Mol Cancer. 23(203)2024.PubMed/NCBI View Article : Google Scholar | |
|
Liu B, Liu L and Liu Y: Targeting cell death mechanisms: The potential of autophagy and ferroptosis in hepatocellular carcinoma therapy. Front Immunol. 15(1450487)2024.PubMed/NCBI View Article : Google Scholar | |
|
Li A, Wang R, Zhao Y, Zhao P and Yang J: Crosstalk between epigenetics and metabolic reprogramming in metabolic dysfunction-associated steatotic liver disease-induced hepatocellular carcinoma: A new sight. Metabolites. 14(325)2024.PubMed/NCBI View Article : Google Scholar | |
|
Nadile M, Sze NS, Fajardo VA and Tsiani E: Inhibition of prostate cancer cell survival and proliferation by carnosic acid is associated with inhibition of Akt and activation of AMPK signaling. Nutrients. 16(1257)2024.PubMed/NCBI View Article : Google Scholar | |
|
Schooling CM, Yang G, Soliman GA and Leung GM: A hypothesis that glucagon-like peptide-1 receptor agonists exert immediate and multifaceted effects by activating adenosine monophosphate-activate protein kinase (AMPK). Life (Basel). 15(253)2025.PubMed/NCBI View Article : Google Scholar | |
|
Manoharan R: Salt-inducible kinases (SIKs) in cancer: Mechanisms of action and therapeutic prospects. Drug Discov Today. 30(104279)2025.PubMed/NCBI View Article : Google Scholar | |
|
Espitia-Pérez PJ, Espitia-Perez LM and Negrette-Guzmán M: Targeting Prostate cancer metabolism through transcriptional and epigenetic modulation: A multi-target approach to therapeutic innovation. Int J Mol Sci. 26(6013)2025.PubMed/NCBI View Article : Google Scholar | |
|
Pujana-Vaquerizo M, Bozal-Basterra L and Carracedo A: Metabolic adaptations in prostate cancer. Br J Cancer. 131:1250–1262. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Feng Y, Zhang Y, Li H, Wang T, Lu F, Liu R, Xie G, Song L, Huang B, Li X, et al: Enzalutamide inhibits PEX10 function and sensitizes prostate cancer cells to ROS activators. Cell Death Dis. 15(559)2024.PubMed/NCBI View Article : Google Scholar | |
|
Lemos G, Fernandes CMADS, Silva FH and Calmasini FB: The role of autophagy in prostate cancer and prostatic diseases: A new therapeutic strategy. Prostate Cancer Prostatic Dis. 27:230–238. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Inoki K, Kim J and Guan KL: AMPK and mTOR in cellular energy homeostasis and drug targets. Annu Rev Pharmacol Toxicol. 52:381–400. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Choi BH and Coloff JL: The diverse functions of non-essential amino acids in cancer. Cancers (Basel). 11(675)2019.PubMed/NCBI View Article : Google Scholar | |
|
Jin J, Byun JK, Choi YK and Park KG: Targeting glutamine metabolism as a therapeutic strategy for cancer. Exp Mol Med. 55:706–715. 2023.PubMed/NCBI View Article : Google Scholar | |
|
Halama A and Suhre K: Advancing cancer treatment by targeting glutamine metabolism-A roadmap. Cancers (Basel). 14(553)2022.PubMed/NCBI View Article : Google Scholar | |
|
Linke M, Fritsch SD, Sukhbaatar N, Hengstschläger M and Weichhart T: mTORC1 and mTORC2 as regulators of cell metabolism in immunity. FEBS Lett. 591:3089–3103. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Wang R, Dillon CP, Shi LZ, Milasta S, Carter R, Finkelstein D, McCormick LL, Fitzgerald P, Chi H, Munger J and Green DR: The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation. Immunity. 35:871–882. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Valvezan AJ and Manning BD: Molecular logic of mTORC1 signalling as a metabolic rheostat. Nat Metab. 1:321–333. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Nishitani S, Horie M, Ishizaki S and Yano H: Branched chain amino acid suppresses hepatocellular cancer stem cells through the activation of mammalian target of rapamycin. PLoS One. 8(e82346)2013.PubMed/NCBI View Article : Google Scholar | |
|
Kazyken D, Magnuson B, Bodur C, Acosta-Jaquez HA, Zhang D, Tong X, Barnes TM, Steinl GK, Patterson NE, Altheim CH, et al: AMPK directly activates mTORC2 to promote cell survival during acute energetic stress. Sci Signal. 12(eaav3249)2019.PubMed/NCBI View Article : Google Scholar | |
|
Sadria M and Layton AT: Interactions among mTORC, AMPK and SIRT: A computational model for cell energy balance and metabolism. Cell Commun Signal. 19(57)2021.PubMed/NCBI View Article : Google Scholar | |
|
Sujobert P, Poulain L, Paubelle E, Zylbersztejn F, Grenier A, Lambert M, Townsend EC, Brusq JM, Nicodeme E, Decrooqc J, et al: Co-activation of AMPK and mTORC1 induces cytotoxicity in acute myeloid leukemia. Cell Rep. 11:1446–1457. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Davie E, Forte GMA and Petersen J: Nitrogen regulates AMPK to control TORC1 signaling. Curr Biol. 25:445–454. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Lie S, Wang T, Forbes B, Proud CG and Petersen J: The ability to utilise ammonia as nitrogen source is cell type specific and intricately linked to GDH, AMPK and mTORC1. Sci Rep. 9(1461)2019.PubMed/NCBI View Article : Google Scholar | |
|
Lu T, Sun L, Wang Z, Zhang Y, He Z and Xu C: Fatty acid synthase enhances colorectal cancer cell proliferation and metastasis via regulating AMPK/mTOR pathway. Onco Targets Ther. 12:3339–3347. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Pereira O, Teixeira A, Sampaio-Marques B, Castro I, Girão H and Ludovico P: Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells. J Cell Mol Med. 22:4807–4817. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Chiang CT, Demetriou AN, Ung N, Choudhury N, Ghaffarian K, Ruderman DL and Mumenthaler SM: mTORC2 contributes to the metabolic reprogramming in EGFR tyrosine-kinase inhibitor resistant cells in non-small cell lung cancer. Cancer Lett. 434:152–159. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Zhang P, Fu HJ, Lv LX, Liu CF, Han C, Zhao XF and Wang JX: WSSV exploits AMPK to activate mTORC2 signaling for proliferation by enhancing aerobic glycolysis. Commun Biol. 6(361)2023.PubMed/NCBI View Article : Google Scholar | |
|
He Z, Houghton PJ, Williams TM and Shen C: Regulation of DNA duplication by the mTOR signaling pathway. Cell Cycle. 20:742–751. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Bu C, Zhao L, Wang L, Yu Z and Zhou J: mTORC2 promotes pancreatic cancer progression and PARP inhibitor resistance. Oncol Res. 31:495–503. 2023.PubMed/NCBI View Article : Google Scholar | |
|
Pournajaf S and Pourgholami MH: The mTOR pathway in Gliomas: From molecular insights to targeted therapies. Biomed Pharmacother. 189(118237)2025.PubMed/NCBI View Article : Google Scholar | |
|
Glaviano A, Foo ASC, Lam HY, Yap KCH, Jacot W, Jones RH, Eng H, Nair MG, Makvandi P, Geoerger B, et al: PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer. Mol Cancer. 22(138)2023.PubMed/NCBI View Article : Google Scholar | |
|
Carew JS, Kelly KR and Nawrocki ST: Mechanisms of mTOR inhibitor resistance in cancer therapy. Target Oncol. 6:17–27. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Dunn S, Eberlein C, Yu J, Gris-Oliver A, Ong SH, Yelland U, Cureton N, Staniszewska A, McEwen R, Fox M, et al: AKT-mTORC1 reactivation is the dominant resistance driver for PI3Kβ/AKT inhibitors in PTEN-null breast cancer and can be overcome by combining with Mcl-1 inhibitors. Oncogene. 41:5046–5060. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Basnet R, Basnet BB, Gupta R, Basnet T, Khadka S and Alam MS: Mammalian target of rapamycin (mTOR) signalling pathway-a potential target for cancer intervention: A short overview. Curr Mol Pharmacol. 17(e310323215268)2024.PubMed/NCBI View Article : Google Scholar | |
|
Kim H, Lebeau B, Papadopoli D, Jovanovic P, Russo M, Avizonis D, Morita M, Afzali F, Ursini-Siegel J, Postovit LM, et al: MTOR modulation induces selective perturbations in histone methylation which influence the anti-proliferative effects of mTOR inhibitors. iScience. 27(109188)2024.PubMed/NCBI View Article : Google Scholar | |
|
Faes S, Santoro T, Troquier L, Silva OD and Dormond O: Rebound pathway overactivation by cancer cells following discontinuation of PI3K or mTOR inhibition promotes cancer cell growth. Biochem Biophys Res Commun. 513:546–552. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Khorasani ABS, Hafezi N, Sanaei MJ, Jafari-Raddani F, Pourbagheri-Sigaroodi A and Bashash D: The PI3K/AKT/mTOR signaling pathway in breast cancer: Review of clinical trials and latest advances. Cell Biochem Funct. 42(e3998)2024.PubMed/NCBI View Article : Google Scholar | |
|
Napolitano F, Lin CC, Ahuja K, Ye D, Chica-Parrado MR, Uemoto Y, Luna P, Matsunaga Y, Mendiratta S, Unni N, et al: Abstract 3003: Targeting mechanisms of adaptive resistance to the PI3Kαmutant selective inhibitor RLY-2608 in HR+/PIK3CA mutant breast cancer. Cancer Res. 85 (8 Suppl 1)(S3003)2025. | |
|
Elkanawati RY, Sumiwi SA and Levita J: Impact of lipids on insulin resistance: Insights from human and animal studies. Drug Des Devel Ther. 18:3337–3360. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Martínez Báez A, Ayala G, Pedroza-Saavedra A, González-Sánchez HM and Chihu Amparan L: Phosphorylation codes in IRS-1 and IRS-2 are associated with the activation/inhibition of insulin canonical signaling pathways. Curr Issues Mol Biol. 46:634–649. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Banjac K, Obradovic M, Zafirovic S, Essack M, Gluvic Z, Sunderic M, Nedic O and Isenovic ER: The involvement of Akt, mTOR, and S6K in the in vivo effect of IGF-1 on the regulation of rat cardiac Na+/K+-ATPase. Mol Biol Rep. 51(517)2024.PubMed/NCBI View Article : Google Scholar | |
|
Wright SCE, Vasilevski N, Serra V, Rodon J and Eichhorn PJA: Mechanisms of resistance to PI3K inhibitors in cancer: Adaptive responses, drug tolerance and cellular plasticity. Cancers (Basel). 13(1538)2021.PubMed/NCBI View Article : Google Scholar | |
|
Pourbarkhordar V, Rahmani S, Roohbakhsh A, Hayes AW and Karimi G: Melatonin effect on breast and ovarian cancers by targeting the PI3K/Akt/mTOR pathway. IUBMB Life. 76:1035–1049. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Vadla R and Haldar D: Mammalian target of rapamycin complex 2 (mTORC2) controls glycolytic gene expression by regulating Histone H3 Lysine 56 acetylation. Cell Cycle. 17:110–123. 2018.PubMed/NCBI View Article : Google Scholar |