Cellular metabolism in pancreatic cancer as a tool for prognosis and treatment (Review)
- Authors:
- Michal Zuzčák
- Jan Trnka
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Affiliations: Department of Biochemistry, Cell and Molecular Biology, Third Faculty of Medicine, Charles University, 10000 Prague, Czech Republic - Published online on: June 20, 2022 https://doi.org/10.3892/ijo.2022.5383
- Article Number: 93
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Copyright: © Zuzčák et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
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|
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Siegel RL, Miller KD, Fuchs HE and Jemal A: Cancer statistics, 2021. CA Cancer J Clin. 71:7–33. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM and Matrisian LM: Projecting cancer incidence and deaths to 2030: The unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 74:2913–2921. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Sarantis P, Koustas E, Papadimitropoulou A, Papavassiliou AG and Karamouzis MV: Pancreatic ductal adenocarcinoma: Treatment hurdles, tumor microenvironment and immunotherapy. World J Gastrointest Oncol. 12:173–181. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Hu JX, Zhao CF, Chen WB, Liu QC, Li QW, Lin YY and Gao F: Pancreatic cancer: A review of epidemiology, trend, and risk factors. World J Gastroenterol. 27:4298–4321. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
McGuigan A, Kelly P, Turkington RC, Jones C, Coleman HG and McCain RS: Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes. World J Gastroenterol. 24:4846–4861. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Vincent A, Herman J, Schulick R, Hruban RH and Goggins M: Pancreatic cancer. Lancet. 378:607–620. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Picozzi VJ, Oh SY, Edwards A, Mandelson MT, Dorer R, Rocha FG, Alseidi A, Biehl T, Traverso LW, Helton WS and Kozarek RA: Five-year actual overall survival in resected pancreatic cancer: A contemporary single-institution experience from a multidisciplinary perspective. Ann Surg Oncol. 24:1722–1730. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, et al: Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 369:1691–1703. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Conroy T, Hammel P, Hebbar M, Ben Abdelghani M, Wei AC, Raoul JL, Choné L, Francois E, Artru P, Biagi JJ, et al: FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med. 379:2395–2406. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Upadhrasta S and Zheng L: Strategies in developing immunotherapy for pancreatic cancer: Recognizing and correcting multiple immune 'defects' in the tumor microenvironment. J Clin Med. 8:14722019. View Article : Google Scholar | |
|
Beatty GL, O'Hara MH, Lacey SF, Torigian DA, Nazimuddin F, Chen F, Kulikovskaya IM, Soulen MC, McGarvey M, Nelson AM, et al: Activity of mesothelin-specific chimeric antigen receptor T cells against pancreatic carcinoma metastases in a phase 1 trial. Gastroenterology. 155:29–32. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
O'Hara M, O'Reilly E, Rosemarie M, Varadhachary G, Wainberg ZA, Ko A, Fisher GA, Rahma O, Lyman JP, Cabanski CR, et al: Abstract CT004: A phase Ib study of CD40 agonistic monoclonal antibody APX005M together with gemcitabine (Gem) and nab-paclitaxel (NP) with or without nivolumab (Nivo) in untreated metastatic ductal pancreatic adenocarcinoma (PDAC) patients. Cancer Res. 79(Suppl 13): CT0042019. View Article : Google Scholar | |
|
Bahary N, Garrido-Laguna I, Cinar P, O'Rourke MA, Somer BG, Nyak-Kapoor A, Lee JS, Munn D, Paul Kennedy E, Vahanian NN, et al: Phase 2 trial of the indoleamine 2,3-dioxygenase pathway (IDO) inhibitor indoximod plus gemcitabine/nab-paclitaxel for the treatment of metastatic pancreas cancer: Interim analysis. J Clin Oncol. 34(Suppl 15): S30202016. View Article : Google Scholar | |
|
Di Federico A, Tateo V, Parisi C, Formica F, Carloni R, Frega G, Rizzo A, Ricci D, Di Marco M, Palloni A and Brandi G: Hacking pancreatic cancer: Present and future of personalized medicine. Pharmaceuticals (Basel). 14:6772021. View Article : Google Scholar | |
|
Yang Y, Liu H, Li Z, Zhao Z, Yip-Schneider M, Fan Q, Schmidt CM, Chiorean EG, Xie J, Cheng L, et al: Role of fatty acid synthase in gemcitabine and radiation resistance of pancreatic cancers. Int J Biochem Mol Biol. 2:89–98. 2011.PubMed/NCBI | |
|
Viale A, Pettazzoni P, Lyssiotis CA, Ying H, Sánchez N, Marchesini M, Carugo A, Green T, Seth S, Giuliani V, et al: Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function. Nature. 514:628–632. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Liu M, Liu W, Qin Y, Xu X, Yu X, Zhuo Q and Ji S: Regulation of metabolic reprogramming by tumor suppressor genes in pancreatic cancer. Exp Hematol Oncol. 9:232020. View Article : Google Scholar | |
|
Daemen A, Peterson D, Sahu N, McCord R, Du X, Liu B, Kowanetz K, Hong R, Moffat J, Gao M, et al: Metabolite profiling stratifies pancreatic ductal adenocarcinomas into subtypes with distinct sensitivities to metabolic inhibitors. Proc Natl Acad Sci USA. 112:E4410–E4417. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Karasinska JM, Topham JT, Kalloger SE, Jang GH, Denroche RE, Culibrk L, Williamson LM, Wong HL, Lee MK, O'Kane GM, et al: Altered gene expression along the glycolysis-cholesterol synthesis axis is associated with outcome in pancreatic cancer. Clin Cancer Res. 26:135–146. 2020. View Article : Google Scholar | |
|
Halbrook CJ and Lyssiotis CA: Employing metabolism to improve the diagnosis and treatment of pancreatic cancer. Cancer Cell. 31:5–19. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Perusina Lanfranca M, Thompson JK, Bednar F, Halbrook C, Lyssiotis C, Levi B and Frankel TL: Metabolism and epigenetics of pancreatic cancer stem cells. Semin Cancer Biol. 57:19–26. 2019. View Article : Google Scholar : | |
|
Perera RM and Bardeesy N: Pancreatic cancer metabolism: Breaking it down to build it back up. Cancer Discov. 5:1247–1261. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Dal Molin M, Zhang M, De Wilde RF, Ottenhof NA, Rezaee N, Wolfgang CL, Blackford A, Vogelstein B, Kinzler KW, Papadopoulos N, et al: Very long-term survival following resection for pancreatic cancer is not explained by commonly mutated genes: Results of whole-exome sequencing analysis. Clin Cancer Res. 21:1944–1950. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Collisson EA, Sadanandam A, Olson P, Gibb WJ, Truitt M, Gu S, Cooc J, Weinkle J, Kim GE, Jakkula L, et al: Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy. Nat Med. 17:500–503. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Moffitt RA, Marayati R, Flate EL, Volmar KE, Loeza SG, Hoadley KA, Rashid NU, Williams LA, Eaton SC, Chung AH, et al: Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. Nat Genet. 47:1168–1178. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Zhao L, Zhao H and Yan H: Gene expression profiling of 1200 pancreatic ductal adenocarcinoma reveals novel subtypes. BMC Cancer. 18:6032018. View Article : Google Scholar : PubMed/NCBI | |
|
Maurer C, Holmstrom SR, He J, Laise P, Su T, Ahmed A, Hibshoosh H, Chabot JA, Oberstein PE, Sepulveda AR, et al: Experimental microdissection enables functional harmonisation of pancreatic cancer subtypes. Gut. 68:1034–1043. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Chan-Seng-Yue M, Kim JC, Wilson GW, Ng K, Figueroa EF, O'Kane GM, Connor AA, Denroche RE, Grant RC, McLeod J, et al: Transcription phenotypes of pancreatic cancer are driven by genomic events during tumor evolution. Nat Genet. 52:231–240. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Lonardo E, Frias-Aldeguer J, Hermann PC and Heeschen C: Pancreatic stellate cells form a niche for cancer stem cells and promote their self-renewal and invasiveness. Cell Cycle. 11:1282–1290. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Richards KE, Zeleniak AE, Fishel ML, Wu J, Littlepage LE and Hill R: Cancer-associated fibroblast exosomes regulate survival and proliferation of pancreatic cancer cells. Oncogene. 36:1770–1778. 2017. View Article : Google Scholar : | |
|
Mejia I, Bodapati S, Chen KT and Díaz B: Pancreatic adenocarcinoma invasiveness and the tumor microenvironment: From biology to clinical trials. Biomedicines. 8:4012020. View Article : Google Scholar : | |
|
Sherman MH, Yu RT, Tseng TW, Sousa CM, Liu S, Truitt ML, He N, Ding N, Liddle C, Atkins AR, et al: Stromal cues regulate the pancreatic cancer epigenome and metabolome. Proc Natl Acad Sci USA. 114:1129–1134. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Sousa CM, Biancur DE, Wang X, Halbrook CJ, Sherman MH, Zhang L, Kremer D, Hwang RF, Witkiewicz AK, Ying H, et al: Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. Nature. 536:479–483. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Tape CJ, Ling S, Dimitriadi M, McMahon KM, Worboys JD, Leong HS, Norrie IC, Miller CJ, Poulogiannis G, Lauffenburger DA and Jørgensen C: Oncogenic KRAS regulates tumor cell signaling via stromal reciprocation. Cell. 165:910–920. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Juiz N, Elkaoutari A, Bigonnet M, Gayet O, Roques J, Nicolle R, Iovanna J and Dusetti N: Basal-like and classical cells coexistence in pancreatic cancer revealed by single cell analysis. bioRxiv. 2020. | |
|
Suzuki T, Otsuka M, Seimiya T, Iwata T, Kishikawa T and Koike K: The biological role of metabolic reprogramming in pancreatic cancer. MedComm (2020). 1:302–310. 2020. | |
|
Zaidi N, Lupien L, Kuemmerle NB, Kinlaw WB, Swinnen JV and Smans K: Lipogenesis and lipolysis: The pathways exploited by the cancer cells to acquire fatty acids. Prog Lipid Res. 52:585–589. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Sancho P, Burgos-Ramos E, Tavera A, Bou Kheir T, Jagust P, Schoenhals M, Barneda D, Sellers K, Campos-Olivas R, Graña O, et al: MYC/PGC-1α balance determines the metabolic phenotype and plasticity of pancreatic cancer stem cells. Cell Metab. 22:590–605. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Kamphorst JJ, Nofal M, Commisso C, Hackett SR, Lu W, Grabocka E, Vander Heiden MG, Miller G, Drebin JA, Bar-Sagi D, et al: Human pancreatic cancer tumors are nutrient poor and tumor cells actively scavenge extracellular protein. Cancer Res. 75:544–553. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Yoshida GJ: Metabolic reprogramming: The emerging concept and associated therapeutic strategies. J Exp Clin Cancer Res. 34:1112015. View Article : Google Scholar : PubMed/NCBI | |
|
Yu M, Zhou Q, Zhou Y, Fu Z, Tan L, Ye X, Zeng B, Gao W, Zhou J, Liu Y, et al: Metabolic phenotypes in pancreatic cancer. PLoS One. 10:e01151532015. View Article : Google Scholar : PubMed/NCBI | |
|
Lomberk G, Blum Y, Nicolle R, Nair A, Gaonkar KS, Marisa L, Mathison A, Sun Z, Yan H, Elarouci N, et al: Distinct epigenetic landscapes underlie the pathobiology of pancreatic cancer subtypes. Nat Commun. 9:19782018. View Article : Google Scholar : PubMed/NCBI | |
|
Kaoutari AE, Fraunhoffer NA, Hoare O, Teyssedou C, Soubeyran P, Gayet O, Roques J, Lomberk G, Urrutia R, Dusetti N and Iovanna J: Metabolomic profiling of pancreatic adenocarcinoma reveals key features driving clinical outcome and drug resistance. EBioMedicine. 66:1033322021. View Article : Google Scholar : PubMed/NCBI | |
|
Liu Q, Ge W, Wang T, Lan J, Martínez-Jarquín S, Wolfrum C, Stoffel M and Zenobi R: High-throughput single-cell mass spectrometry reveals abnormal lipid metabolism in pancreatic ductal adenocarcinoma. Angew Chem Int Ed Engl. 60:24534–24542. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Argüello RJ, Combes AJ, Char R, Gigan JP, Baaziz AI, Bousiquot E, Camosseto V, Samad B, Tsui J, Yan P, et al: SCENITH: A flow cytometry-based method to functionally profile energy metabolism with single-cell resolution. Cell Metab. 32:1063–1075.e7. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Miller A, Nagy C, Knapp B, Laengle J, Ponweiser E, Groeger M, Starkl P, Bergmann M, Wagner O and Haschemi A: Exploring metabolic configurations of single cells within complex tissue microenvironments. Cell Metab. 26:788–800.e6. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Ambrosini G, Dalla Pozza E, Fanelli G, Di Carlo C, Vettori A, Cannino G, Cavallini C, Carmona-Carmona CA, Brandi J, Rinalducci S, et al: Progressively de-differentiated pancreatic cancer cells shift from glycolysis to oxidative metabolism and gain a quiescent stem state. Cells. 9:15722020. View Article : Google Scholar : | |
|
Biancur DE, Paulo JA, Małachowska B, Quiles Del Rey M, Sousa CM, Wang X, Sohn ASW, Chu GC, Gygi SP, Harper JW, et al: Compensatory metabolic networks in pancreatic cancers upon perturbation of glutamine metabolism. Nat Commun. 8:159652017. View Article : Google Scholar : PubMed/NCBI | |
|
Koppenol WH, Bounds PL and Dang CV: Otto Warburg's contributions to current concepts of cancer metabolism. Nat Rev Cancer. 11:325–337. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Liu XS, Little JB and Yuan ZM: Glycolytic metabolism influences global chromatin structure. Oncotarget. 6:4214–4225. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Liberti MV and Locasale JW: The Warburg effect: How does it benefit cancer cells? Trends Biochem Sci. 41:211–218. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Husain Z, Huang Y, Seth P and Sukhatme VP: Tumor-derived lactate modifies antitumor immune response: Effect on myeloid-derived suppressor cells and NK cells. J Immunol. 191:1486–1495. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Du J, Gu J, Deng J, Kong L, Guo Y, Jin C, Bao Y, Fu D and Li J: The expression and survival significance of glucose transporter-1 in pancreatic cancer: Meta-analysis, bioinformatics analysis and retrospective study. Cancer Invest. 39:741–755. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Lee EE, Ma J, Sacharidou A, Mi W, Salato VK, Nguyen N, Jiang Y, Pascual JM, North PE, Shaul PW, et al: A protein kinase C phosphorylation motif in GLUT1 affects glucose transport and is mutated in GLUT1 deficiency syndrome. Mol Cell. 58:845–853. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Cheng CS, Tan HY, Wang N, Chen L, Meng Z, Chen Z and Feng Y: Functional inhibition of lactate dehydrogenase suppresses pancreatic adenocarcinoma progression. Clin Transl Med. 11:e4672021. View Article : Google Scholar : PubMed/NCBI | |
|
Ying H, Kimmelman AC, Lyssiotis CA, Hua S, Chu GC, Fletcher-Sananikone E, Locasale JW, Son J, Zhang H, Coloff JL, et al: Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell. 149:656–670. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Jiang W, Qiao L, Zuo D, Qin D, Xiao J, An H, Wang Y, Zhang X, Jin Y and Ren L: Aberrant lactate dehydrogenase A signaling contributes metabolic signatures in pancreatic cancer. Ann Transl Med. 9:3582021. View Article : Google Scholar : PubMed/NCBI | |
|
Yalcin A, Solakoglu TH, Ozcan SC, Guzel S, Peker S, Celikler S, Balaban BD, Sevinc E, Gurpinar Y and Chesney JA: 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase-3 is required for transforming growth factor β1-enhanced invasion of Panc1 cells in vitro. Biochem Biophys Res Commun. 484:687–693. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Ji S, Zhang B, Liu J, Qin Y, Liang C, Shi S, Jin K, Liang D, Xu W, Xu H, et al: ALDOA functions as an oncogene in the highly metastatic pancreatic cancer. Cancer Lett. 374:127–135. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Principe M, Borgoni S, Cascione M, Chattaragada MS, Ferri-Borgogno S, Capello M, Bulfamante S, Chapelle J, Di Modugno F, Defilippi P, et al: Alpha-enolase (ENO1) controls alpha v/beta 3 integrin expression and regulates pancreatic cancer adhesion, invasion, and metastasis. J Hematol Oncol. 10:162017. View Article : Google Scholar : PubMed/NCBI | |
|
Principe M, Ceruti P, Shih NY, Chattaragada MS, Rolla S, Conti L, Bestagno M, Zentilin L, Yang SH, Migliorini P, et al: Targeting of surface alpha-enolase inhibits the invasiveness of pancreatic cancer cells. Oncotarget. 6:11098–11113. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Azoitei N, Becher A, Steinestel K, Rouhi A, Diepold K, Genze F, Simmet T and Seufferlein T: PKM2 promotes tumor angiogenesis by regulating HIF-1α through NF-κB activation. Mol Cancer. 15:32016. View Article : Google Scholar | |
|
Thews O and Riemann A: Tumor pH and metastasis: A malignant process beyond hypoxia. Cancer Metastasis Rev. 38:113–129. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Guillaumond F, Leca J, Olivares O, Lavaut MN, Vidal N, Berthezène P, Dusetti NJ, Loncle C, Calvo E, Turrini O, et al: Strengthened glycolysis under hypoxia supports tumor symbiosis and hexosamine biosynthesis in pancreatic adenocarcinoma. Proc Natl Acad Sci USA. 110:3919–3924. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Kirk P, Wilson MC, Heddle C, Brown MH, Barclay AN and Halestrap AP: CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression. EMBO J. 19:3896–3904. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Semenza GL: Tumor metabolism: Cancer cells give and take lactate. J Clin Invest. 118:3835–3837. 2008.PubMed/NCBI | |
|
Sun X, Wang M, Wang M, Yao L, Li X, Dong H, Li M, Sun T, Liu X, Liu Y and Xu Y: Role of proton-coupled monocarboxylate transporters in cancer: From metabolic crosstalk to therapeutic potential. Front cell Dev Biol. 8:6512020. View Article : Google Scholar : PubMed/NCBI | |
|
Pavlides S, Whitaker-Menezes D, Castello-Cros R, Flomenberg N, Witkiewicz AK, Frank PG, Casimiro MC, Wang C, Fortina P, Addya S, et al: The reverse Warburg effect: Aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. Cell Cycle. 8:3984–4001. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Benny S, Mishra R, Manojkumar MK and Aneesh TP: From Warburg effect to reverse Warburg effect; the new horizons of anti-cancer therapy. Med Hypotheses. 144:1102162020. View Article : Google Scholar : PubMed/NCBI | |
|
Roland CL, Arumugam T, Deng D, Liu SH, Philip B, Gomez S, Burns WR, Ramachandran V, Wang H, Cruz-Monserrate Z and Logsdon CD: Cell surface lactate receptor GPR81 is crucial for cancer cell survival. Cancer Res. 74:5301–5310. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Benton CR, Yoshida Y, Lally J, Han X-X, Hatta H and Bonen A: PGC-1alpha increases skeletal muscle lactate uptake by increasing the expression of MCT1 but not MCT2 or MCT4. Physiol Genomics. 35:45–54. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Cheng CF, Ku HC and Lin H: PGC-1α as a pivotal factor in lipid and metabolic regulation. Int J Mol Sci. 19:34472018. View Article : Google Scholar | |
|
Schneiderhan W, Scheler M, Holzmann KH, Marx M, Gschwend JE, Bucholz M, Gress TM, Seufferlein T, Adler G and Oswald F: CD147 silencing inhibits lactate transport and reduces malignant potential of pancreatic cancer cells in in vivo and in vitro models. Gut. 58:1391–1398. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Lee SH, Hwang HK, Lee WJ and Kang CM: MCT4 as a potential therapeutic target to augment gemcitabine chemosensitivity in resected pancreatic cancer. Cell Oncol (Dordr). 44:1363–1371. 2021. View Article : Google Scholar | |
|
Benjamin D, Robay D, Hindupur SK, Pohlmann J, Colombi M, El-Shemerly MY, Maira SM, Moroni C, Lane HA and Hall MN: Dual inhibition of the lactate transporters MCT1 and MCT4 Is synthetic lethal with metformin due to NAD+ depletion in cancer cells. Cell Rep. 25:3047–3058.e4. 2018. View Article : Google Scholar | |
|
Sonveaux P, Végran F, Schroeder T, Wergin MC, Verrax J, Rabbani ZN, De Saedeleer CJ, Kennedy KM, Diepart C, Jordan BF, et al: Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J Clin Invest. 118:3930–3942. 2008.PubMed/NCBI | |
|
Wu DH, Liang H, Lu SN, Wang H, Su ZL, Zhang L, Ma JQ, Guo M, Tai S and Yu S: miR-124 suppresses pancreatic ductal adenocarcinoma growth by regulating monocarboxylate transporter 1-mediated cancer lactate metabolism. Cell Physiol Biochem. 50:924–935. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Lau AN, Li Z, Danai LV, Westermark AM, Darnell AM, Ferreira R, Gocheva V, Sivanand S, Lien EC, Sapp KM, et al: Dissecting cell-type-specific metabolism in pancreatic ductal adenocarcinoma. Elife. 9:e567822020. View Article : Google Scholar : PubMed/NCBI | |
|
Koundouros N and Poulogiannis G: Reprogramming of fatty acid metabolism in cancer. Br J Cancer. 122:4–22. 2020. View Article : Google Scholar : | |
|
Alo PL, Amini M, Piro F, Pizzuti L, Sebastiani V, Botti C, Murari R, Zotti G and Di Tondo U: Immunohistochemical expression and prognostic significance of fatty acid synthase in pancreatic carcinoma. Anticancer Res. 27:2523–2527. 2007.PubMed/NCBI | |
|
Li N, Lu H, Chen C, Bu X and Huang P: Loss of fatty acid synthase inhibits the 'hER2-PI3K/Akt axis' activity and malignant phenotype of Caco-2 cells. Lipids Health Dis. 12:832013. View Article : Google Scholar | |
|
Menendez JA, Decker JP and Lupu R: In support of fatty acid synthase (FAS) as a metabolic oncogene: Extracellular acidosis acts in an epigenetic fashion activating FAS gene expression in cancer cells. J Cell Biochem. 94:1–4. 2005. View Article : Google Scholar | |
|
Shetty A, Nagesh PKB, Setua S, Hafeez BB, Jaggi M, Yallapu MM and Chauhan SC: Novel paclitaxel nanoformulation impairs de novo lipid synthesis in pancreatic cancer cells and enhances gemcitabine efficacy. ACS Omega. 5:8982–8991. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Tracz-Gaszewska Z and Dobrzyn P: Stearoyl-CoA desaturase 1 as a therapeutic target for the treatment of cancer. Cancers (Basel). 11:9482019. View Article : Google Scholar | |
|
Rysman E, Brusselmans K, Scheys K, Timmermans L, Derua R, Munck S, Van Veldhoven PP, Waltregny D, Daniëls VW, Machiels J, et al: De novo lipogenesis protects cancer cells from free radicals and chemotherapeutics by promoting membrane lipid saturation. Cancer Res. 70:8117–8126. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Fritz V, Benfodda Z, Rodier G, Henriquet C, Iborra F, Avancès C, Allory Y, de la Taille A, Culine S, Blancou H, et al: Abrogation of de novo lipogenesis by stearoyl-CoA desaturase 1 inhibition interferes with oncogenic signaling and blocks prostate cancer progression in mice. Mol Cancer Ther. 9:1740–1754. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Eser S, Schnieke A, Schneider G and Saur D: Oncogenic KRAS signalling in pancreatic cancer. Br J Cancer. 111:817–822. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Menendez JA: Fine-tuning the lipogenic/lipolytic balance to optimize the metabolic requirements of cancer cell growth: Molecular mechanisms and therapeutic perspectives. Biochim Biophys Acta. 1801:381–391. 2010. View Article : Google Scholar | |
|
Xu M, Jung X, Hines OJ, Eibl G and Chen Y: Obesity and pancreatic cancer: Overview of epidemiology and potential prevention by weight loss. Pancreas. 47:158–162. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Li D, Morris JS, Liu J, Hassan MM, Day RS, Bondy ML and Abbruzzese JL: Body mass index and risk, age of onset, and survival in patients with pancreatic cancer. JAMA. 301:2553–2562. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Kasenda B, Bass A, Koeberle D, Pestalozzi B, Borner M, Herrmann R, Jost L, Lohri A and Hess V: Survival in overweight patients with advanced pancreatic carcinoma: A multicentre cohort study. BMC Cancer. 14:7282014. View Article : Google Scholar : PubMed/NCBI | |
|
Anderson AS, Renehan AG, Saxton JM, Bell J, Cade J, Cross AJ, King A, Riboli E, Sniehotta F, Treweek S, et al: Cancer prevention through weight control-where are we in 2020? Br J Cancer. 124:1049–1056. 2021. View Article : Google Scholar | |
|
Jacobs EJ, Newton CC, Patel AV, Stevens VL, Islami F, Flanders WD and Gapstur SM: The association between body mass index and pancreatic cancer: Variation by age at body mass index assessment. Am J Epidemiol. 189:108–115. 2020. View Article : Google Scholar | |
|
Chimento A, Casaburi I, Avena P, Trotta F, De Luca A, Rago V, Pezzi V and Sirianni R: Cholesterol and its metabolites in tumor growth: Therapeutic potential of statins in cancer treatment. Front Endocrinol (Lausanne). 9:8072019. View Article : Google Scholar | |
|
Guillaumond F, Bidaut G, Ouaissi M, Servais S, Gouirand V, Olivares O, Lac S, Borge L, Roques J, Gayet O, et al: Cholesterol uptake disruption, in association with chemotherapy, is a promising combined metabolic therapy for pancreatic adenocarcinoma. Proc Natl Acad Sci USA. 112:2473–2478. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Nam GH, Kwon M, Jung H, Ko E, Kim SA, Choi Y, Song SJ, Kim S, Lee Y, Kim GB, et al: Statin-mediated inhibition of RAS prenylation activates ER stress to enhance the immunogenicity of KRAS mutant cancer. J Immunother cancer. 9:e0024742021. View Article : Google Scholar : PubMed/NCBI | |
|
Jiang W, Hu JW, He XR, Jin WL and He XY: Statins: A repurposed drug to fight cancer. J Exp Clin Cancer Res. 40:2412021. View Article : Google Scholar : PubMed/NCBI | |
|
Osmak M: Statins and cancer: Current and future prospects. Cancer Lett. 324:1–12. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Kawata S, Yamasaki E, Nagase T, Inui Y, Ito N, Matsuda Y, Inada M, Tamura S, Noda S, Imai Y and Matsuzawa Y: Effect of pravastatin on survival in patients with advanced hepatocellular carcinoma. A randomized controlled trial. Br J Cancer. 84:886–891. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Lersch C, Schmelz R, Erdmann J, Hollweck R, Schulte-Frohlinde E, Eckel F, Nader M and Schusdziarra V: Treatment of HCC with pravastatin, octreotide, or gemcitabine-a critical evaluation. Hepatogastroenterology. 51:1099–1103. 2004.PubMed/NCBI | |
|
Butera A, Roy M, Zampieri C, Mammarella E, Panatta E, Melino G, D'Alessandro A and Amelio I: p53-driven lipidome influences non-cell-autonomous lysophospholipids in pancreatic cancer. Biol Direct. 17:62022. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang L, Jin H, Guo X, Yang Z, Zhao L, Tang S, Mo P, Wu K, Nie Y, Pan Y and Fan D: Distinguishing pancreatic cancer from chronic pancreatitis and healthy individuals by (1)H nuclear magnetic resonance-based metabonomic profiles. Clin Biochem. 45:1064–1069. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Urayama S, Zou W, Brooks K and Tolstikov V: Comprehensive mass spectrometry based metabolic profiling of blood plasma reveals potent discriminatory classifiers of pancreatic cancer. Rapid Commun Mass Spectrom. 24:613–620. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Wang G, Yao H, Gong Y, Lu Z, Pang R, Li Y, Yung Y, Song H, Liu J, Jin Y, et al: Metabolic detection and systems analyses of pancreatic ductal adenocarcinoma through machine learning, lipidomics, and multi-omics. Sci Adv. 7:eabh27242021. View Article : Google Scholar : PubMed/NCBI | |
|
Fang F, He X, Deng H, Chen Q, Lu J, Spraul M and Yu Y: Discrimination of metabolic profiles of pancreatic cancer from chronic pancreatitis by high-resolution magic angle spinning 1H nuclear magnetic resonance and principal components analysis. Cancer Sci. 98:1678–1682. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Z, Liu F, Fan N, Zhou C, Li D, Macvicar T, Dong Q, Bruns CJ and Zhao Y: Targeting glutaminolysis: New perspectives to understand cancer development and novel strategies for potential target therapies. Front Oncol. 10:5895082020. View Article : Google Scholar : PubMed/NCBI | |
|
DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S and Thompson CB: Beyond aerobic glycolysis: Transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci USA. 104:19345–19350. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Ghanem N, El-Baba C, Araji K, El-Khoury R, Usta J and Darwiche N: The pentose phosphate pathway in cancer: Regulation and therapeutic opportunities. Chemotherapy. 66:179–191. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Ju HQ, Lin JF, Tian T, Xie D and Xu RH: NADPH homeostasis in cancer: Functions, mechanisms and therapeutic implications. Signal Transduct Target Ther. 5:2312020. View Article : Google Scholar : PubMed/NCBI | |
|
Badgley MA, Kremer DM, Maurer HC, DelGiorno KE, Lee HJ, Purohit V, Sagalovskiy IR, Ma A, Kapilian J, Firl CEM, et al: Cysteine depletion induces pancreatic tumor ferroptosis in mice. Science. 368:85–89. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Hatzivassiliou G, Zhao F, Bauer DE, Andreadis C, Shaw AN, Dhanak D, Hingorani SR, Tuveson DA and Thompson CB: ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell. 8:311–321. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Akella NM, Ciraku L and Reginato MJ: Fueling the fire: Emerging role of the hexosamine biosynthetic pathway in cancer. BMC Biol. 17:522019. View Article : Google Scholar : PubMed/NCBI | |
|
Tong X, Zhao F and Thompson CB: The molecular determinants of de novo nucleotide biosynthesis in cancer cells. Curr Opin Genet Dev. 19:32–37. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Y, Bai C, Ruan Y, Liu M, Chu Q, Qiu L, Yang C and Li B: Coordinative metabolism of glutamine carbon and nitrogen in proliferating cancer cells under hypoxia. Nat Commun. 10:2012019. View Article : Google Scholar : PubMed/NCBI | |
|
Bott AJ, Shen J, Tonelli C, Zhan L, Sivaram N, Jiang YP, Yu X, Bhatt V, Chiles E, Zhong H, et al: Glutamine anabolism plays a critical role in pancreatic cancer by coupling carbon and nitrogen metabolism. Cell Rep. 29:1287–1298.e6. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Li T and Le A: Glutamine metabolism in cancer. The Heterogeneity of Cancer Metabolism. Le A: Springer International Publishing; Cham: pp. 13–32. 2018, View Article : Google Scholar | |
|
Son J, Lyssiotis CA, Ying H, Wang X, Hua S, Ligorio M, Perera RM, Ferrone CR, Mullarky E, Shyh-Chang N, et al: Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature. 496:101–105. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Li W, Chen C, Zhao X, Ye H, Zhao Y, Fu Z, Pan W, Zheng S, Wei L, Nong T, et al: HIF-2α regulates non-canonical glutamine metabolism via activation of PI3K/mTORC2 pathway in human pancreatic ductal adenocarcinoma. J Cell Mol Med. 21:2896–2908. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Raho S, Capobianco L, Malivindi R, Vozza A, Piazzolla C, De Leonardis F, Gorgoglione R, Scarcia P, Pezzuto F, Agrimi G, et al: KRAS-regulated glutamine metabolism requires UCP2-mediated aspartate transport to support pancreatic cancer growth. Nat Metab. 2:1373–1381. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Yang S, Hwang S, Kim M, Seo SB, Lee JH and Jeong SM: Mitochondrial glutamine metabolism via GOT2 supports pancreatic cancer growth through senescence inhibition. Cell Death Dis. 9:552018. View Article : Google Scholar : PubMed/NCBI | |
|
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. View Article : Google Scholar : PubMed/NCBI | |
|
Gao P, Tchernyshyov I, Chang TC, Lee YS, Kita K, Ochi T, Zeller KI, De Marzo AM, Van Eyk JE, Mendell JT and Dang CV: c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature. 458:762–765. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Roux C, Riganti C, Borgogno SF, Curto R, Curcio C, Catanzaro V, Digilio G, Padovan S, Puccinelli MP, Isabello M, et al: Endogenous glutamine decrease is associated with pancreatic cancer progression. Oncotarget. 8:95361–95376. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
He J, Li F, Zhou Y, Hou X, Liu S, Li X, Zhang Y, Jing X and Yang L: LncRNA XLOC_006390 promotes pancreatic carcinogenesis and glutamate metabolism by stabilizing c-Myc. Cancer Lett. 469:419–428. 2020. View Article : Google Scholar | |
|
Lowman XH, Hanse EA, Yang Y, Ishak Gabra MB, Tran TQ, Li H and Kong M: p53 Promotes cancer cell adaptation to glutamine deprivation by upregulating Slc7a3 to increase arginine uptake. Cell Rep. 26:3051–3060.e4. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Tajan M, Hock AK, Blagih J, Robertson NA, Labuschagne CF, Kruiswijk F, Humpton TJ, Adams PD and Vousden KH: A role for p53 in the adaptation to glutamine starvation through the expression of SLC1A3. Cell Metab. 28:721–736.e6. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Tran TQ, Lowman XH, Reid MA, Mendez-Dorantes C, Pan M, Yang Y and Kong M: Tumor-associated mutant p53 promotes cancer cell survival upon glutamine deprivation through p21 induction. Oncogene. 36:1991–2001. 2017. View Article : Google Scholar : | |
|
Dey P, Baddour J, Muller F, Wu CC, Wang H, Liao WT, Lan Z, Chen A, Gutschner T, Kang Y, et al: Genomic deletion of malic enzyme 2 confers collateral lethality in pancreatic cancer. Nature. 542:119–123. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Dai Z, Ramesh V and Locasale JW: The evolving metabolic landscape of chromatin biology and epigenetics. Nat Rev Genet. 21:737–753. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Wang G and Han JJ: Connections between metabolism and epigenetic modifications in cancer. Med Rev. 1:199–221. 2021. View Article : Google Scholar | |
|
Etchegaray JP and Mostoslavsky R: Interplay between metabolism and epigenetics: A nuclear adaptation to environmental changes. Mol Cell. 62:695–711. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Kottakis F, Nicolay BN, Roumane A, Karnik R, Gu H, Nagle JM, Boukhali M, Hayward MC, Li YY, Chen T, et al: LKB1 loss links serine metabolism to DNA methylation and tumorigenesis. Nature. 539:390–395. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Wang H, Li QF, Chow H, Choi S and Leung YC: Arginine deprivation inhibits pancreatic cancer cell migration, invasion and EMT via the down regulation of snail, slug, twist, and MMP1/9. J Physiol Biochem. 76:73–83. 2020. View Article : Google Scholar | |
|
Wang J, Yang S, He P, Schetter AJ, Gaedcke J, Ghadimi BM, Ried T, Yfantis HG, Lee DH, Gaida MM, et al: Endothelial nitric oxide synthase traffic inducer (NOSTRIN) is a negative regulator of disease aggressiveness in pancreatic cancer. Clin Cancer Res. 22:5992–6001. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Herner A, Sauliunaite D, Michalski CW, Erkan M, De Oliveira T, Abiatari I, Kong B, Esposito I, Friess H and Kleeff J: Glutamate increases pancreatic cancer cell invasion and migration via AMPA receptor activation and Kras-MAPK signaling. Int J Cancer. 129:2349–2359. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Gitto SB, Pandey V, Oyer JL, Copik AJ, Hogan FC, Phanstiel O IV and Altomare DA: Difluoromethylornithine combined with a polyamine transport inhibitor is effective against gemcitabine resistant pancreatic cancer. Mol Pharm. 15:369–376. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Kremer JC, Prudner BC, Lange SES, Bean GR, Schultze MB, Brashears CB, Radyk MD, Redlich N, Tzeng SC, Kami K, et al: Arginine deprivation inhibits the Warburg effect and upregulates glutamine anaplerosis and serine biosynthesis in ASS1-deficient cancers. Cell Rep. 18:991–1004. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Davidson SM, Jonas O, Keibler MA, Hou HW, Luengo A, Mayers JR, Wyckoff J, Del Rosario AM, Whitman M, Chin CR, et al: Direct evidence for cancer-cell-autonomous extracellular protein catabolism in pancreatic tumors. Nat Med. 23:235–241. 2017. View Article : Google Scholar | |
|
Maertin S, Elperin JM, Lotshaw E, Sendler M, Speakman SD, Takakura K, Reicher BM, Mareninova OA, Grippo PJ, Mayerle J, et al: Roles of autophagy and metabolism in pancreatic cancer cell adaptation to environmental challenges. Am J Physiol Gastrointest Liver Physiol. 313:G524–G536. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Saliakoura M, Sebastiano MR, Nikdima I, Pozzato C and Konstantinidou G: Restriction of extracellular lipids renders pancreatic cancer dependent on autophagy. J Exp Clin Cancer Res. 41:162022. View Article : Google Scholar : PubMed/NCBI | |
|
Piffoux M, Eriau E and Cassier PA: Autophagy as a therapeutic target in pancreatic cancer. Br J Cancer. 124:333–344. 2021. View Article : Google Scholar : | |
|
Li J, Chen X, Kang R, Zeh H, Klionsky DJ and Tang D: Regulation and function of autophagy in pancreatic cancer. Autophagy. 17:3275–3296. 2021. View Article : Google Scholar : | |
|
Yamamoto K, Venida A, Yano J, Biancur DE, Kakiuchi M, Gupta S, Sohn ASW, Mukhopadhyay S, Lin EY, Parker SJ, et al: Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I. Nature. 581:100–105. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Mukhopadhyay S, Biancur DE, Parker SJ, Yamamoto K, Banh RS, Paulo JA, Mancias JD and Kimmelman AC: Autophagy is required for proper cysteine homeostasis in pancreatic cancer through regulation of SLC7A11. Proc Natl Acad Sci USA. 118:e20214751182021. View Article : Google Scholar : PubMed/NCBI | |
|
Ashton TM, Gillies McKenna W, Kunz-Schughart LA and Higgins GS: Oxidative phosphorylation as an emerging target in cancer therapy. Clin Cancer Res. 24:2482–2490. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Zong WX, Rabinowitz JD and White E: Mitochondria and cancer. Mol Cell. 61:667–676. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Lambert A and Brand M: Reactive oxygen species production by mitochondria. Methods Mol Biol. 554:165–181. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Weinberg F, Hamanaka R, Wheaton WW, Weinberg S, Joseph J, Lopez M, Kalyanaraman B, Mutlu GM, Budinger GR and Chandel NS: Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc Natl Acad Sci USA. 107:8788–8793. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Nevala-Plagemann C, Hidalgo M and Garrido-Laguna I: From state-of-the-art treatments to novel therapies for advanced-stage pancreatic cancer. Nat Rev Clin Oncol. 17:108–123. 2020. View Article : Google Scholar | |
|
Masoud R, Reyes-Castellanos G, Lac S, Garcia J, Dou S, Shintu L, Abdel Hadi N, Gicquel T, El Kaoutari A, Diémé B, et al: Targeting mitochondrial complex I overcomes chemoresistance in high OXPHOS pancreatic cancer. Cell Rep Med. 1:1001432020. View Article : Google Scholar : PubMed/NCBI | |
|
Candido S, Abrams SL, Steelman L, Lertpiriyapong K, Martelli AM, Cocco L, Ratti S, Follo MY, Murata RM, Rosalen PL, et al: Metformin influences drug sensitivity in pancreatic cancer cells. Adv Biol Regul. 68:13–30. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Zannella VE, Dal Pra A, Muaddi H, McKee TD, Stapleton S, Sykes J, Glicksman R, Chaib S, Zamiara P, Milosevic M, et al: Reprogramming metabolism with metformin improves tumor oxygenation and radiotherapy response. Clin Cancer Res. 19:6741–6750. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Neesse A, Bauer CA, Öhlund D, Lauth M, Buchholz M, Michl P, Tuveson DA and Gress TM: Stromal biology and therapy in pancreatic cancer: Ready for clinical translation? Gut. 68:159–171. 2019. View Article : Google Scholar | |
|
Croucher DR, Saunders DN, Lobov S and Ranson M: Revisiting the biological roles of PAI2 (SERPINB2) in cancer. Nat Rev Cancer. 8:535–545. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Harris NLE, Vennin C, Conway JRW, Vine KL, Pinese M, Cowley MJ, Shearer RF, Lucas MC, Herrmann D, Allam AH, et al: SerpinB2 regulates stromal remodelling and local invasion in pancreatic cancer. Oncogene. 36:4288–4298. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Jiang B, Zhou L, Lu J, Wang Y, Liu C, You L and Guo J: Stroma-targeting therapy in pancreatic cancer: One coin with two sides? Front Oncol. 10:5763992020. View Article : Google Scholar : PubMed/NCBI | |
|
Rhim AD, Oberstein PE, Thomas DH, Mirek ET, Palermo CF, Sastra SA, Dekleva EN, Saunders T, Becerra CP, Tattersall IW, et al: Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma. Cancer Cell. 25:735–747. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
de la Fouchardière C, Gamradt P, Chabaud S, Raddaz M, Blanc E, Msika O, Treilleux I, Bachy S, Cattey-Javouhey A, Guibert P, et al: A promising biomarker and therapeutic target in patients with advanced PDAC: The stromal protein βig-h3. J Pers Med. 12:6232022. View Article : Google Scholar | |
|
Olive KP, Jacobetz MA, Davidson CJ, Gopinathan A, McIntyre D, Honess D, Madhu B, Goldgraben MA, Caldwell ME, Allard D, et al: Inhibition of hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science. 324:1457–1461. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Bulle A and Lim KH: Beyond just a tight fortress: Contribution of stroma to epithelial-mesenchymal transition in pancreatic cancer. Signal Transduct Target Ther. 5:2492020. View Article : Google Scholar : PubMed/NCBI | |
|
Malchiodi ZX, Cao H, Gay MD, Safronenka A, Bansal S, Tucker RD, Weinberg BA, Cheema A, Shivapurkar N and Smith JP: Cholecystokinin receptor antagonist improves efficacy of chemotherapy in murine models of pancreatic cancer by altering the tumor microenvironment. Cancers (Basel). 13:49492021. View Article : Google Scholar | |
|
Lee JJ, Perera RM, Wang H, Wu DC, Liu XS, Han S, Fitamant J, Jones PD, Ghanta KS, Kawano S, et al: Stromal response to hedgehog signaling restrains pancreatic cancer progression. Proc Natl Acad Sci USA. 111:E3091–E3100. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Wu Y, Zhang C, Jiang K, Werner J, Bazhin AV and D'Haese JG: The role of stellate cells in pancreatic ductal adenocarcinoma: Targeting perspectives. Front Oncol. 10:6219372021. View Article : Google Scholar : PubMed/NCBI | |
|
Lisanti MP, Martinez-Outschoorn UE, Chiavarina B, Pavlides S, Whitaker-Menezes D, Tsirigos A, Witkiewicz A, Lin Z, Balliet R, Howell A and Sotgia F: Understanding the 'lethal' drivers of tumor-stroma co-evolution: Emerging role(s) for hypoxia, oxidative stress and autophagy/mitophagy in the tumor micro-environment. Cancer Biol Ther. 10:537–542. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Ko YH, Lin Z, Flomenberg N, Pestell RG, Howell A, Sotgia F, Lisanti MP and Martinez-Outschoorn UE: Glutamine fuels a vicious cycle of autophagy in the tumor stroma and oxidative mitochondrial metabolism in epithelial cancer cells: Implications for preventing chemotherapy resistance. Cancer Biol Ther. 12:1085–1097. 2011. View Article : Google Scholar | |
|
Mariño G and Kroemer G: Ammonia: A diffusible factor released by proliferating cells that induces autophagy. Sci Signal. 3:pe192010. View Article : Google Scholar : PubMed/NCBI | |
|
Zhao H, Yang L, Baddour J, Achreja A, Bernard V, Moss T, Marini JC, Tudawe T, Seviour EG, San Lucas FA, et al: Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism. Elife. 5:e102502016. View Article : Google Scholar : PubMed/NCBI | |
|
Waldenmaier M, Seibold T, Seufferlein T and Eiseler T: Pancreatic cancer small extracellular vesicles (exosomes): A tale of short- and long-distance communication. Cancers (Basel). 13:48442021. View Article : Google Scholar | |
|
Takikawa T, Masamune A, Yoshida N, Hamada S, Kogure T and Shimosegawa T: Exosomes derived from pancreatic stellate cells: MicroRNA signature and effects on pancreatic cancer cells. Pancreas. 46:19–27. 2017. View Article : Google Scholar | |
|
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. View Article : Google Scholar : PubMed/NCBI | |
|
Olivares O, Mayers JR, Gouirand V, Torrence ME, Gicquel T, Borge L, Lac S, Roques J, Lavaut MN, Berthezène P, et al: Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions. Nat Commun. 8:160312017. View Article : Google Scholar : PubMed/NCBI | |
|
Begum A, McMillan RH, Chang YT, Penchev VR, Rajeshkumar NV, Maitra A, Goggins MG, Eshelman JR, Wolfgang CL, Rasheed ZA and Matsui W: Direct interactions with cancer-associated fibroblasts lead to enhanced pancreatic cancer stem cell function. Pancreas. 48:329–334. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Cai Z, Liang Y, Xing C, Wang H, Hu P, Li J, Huang H, Wang W and Jiang C: Cancer-associated adipocytes exhibit distinct phenotypes and facilitate tumor progression in pancreatic cancer. Oncol Rep. 42:2537–2549. 2019.PubMed/NCBI | |
|
Meyer KA, Neeley CK, Baker NA, Washabaugh AR, Flesher CG, Nelson BS, Frankel TL, Lumeng CN, Lyssiotis CA, Wynn ML, et al: Adipocytes promote pancreatic cancer cell proliferation via glutamine transfer. Biochem Biophys Rep. 7:144–149. 2016.PubMed/NCBI | |
|
Ye H, Zhou Q, Zheng S, Li G, Lin Q, Wei L, Fu Z, Zhang B, Liu Y, Li Z and Chen R: Tumor-associated macrophages promote progression and the Warburg effect via CCL18/NF-kB/VCAM-1 pathway in pancreatic ductal adenocarcinoma. Cell Death Dis. 9:4532018. View Article : Google Scholar : PubMed/NCBI | |
|
Asencio-Barría C, Defamie N, Sáez JC, Mesnil M and Godoy AS: Direct intercellular communications and cancer: A snapshot of the biological roles of connexins in prostate cancer. Cancers (Basel). 11:13702019. View Article : Google Scholar | |
|
Luo M, Luo Y, Mao N, Huang G, Teng C, Wang H, Wu J, Liao X and Yang J: Cancer-associated fibroblasts accelerate malignant progression of non-small cell lung cancer via connexin 43-formed unidirectional gap junctional intercellular communication. Cell Physiol Biochem. 51:315–336. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Wang J, Liu X, Qiu Y, Shi Y, Cai J, Wang B, Wei X, Ke Q, Sui X, Wang Y, et al: Cell adhesion-mediated mitochondria transfer contributes to mesenchymal stem cell-induced chemoresistance on T cell acute lymphoblastic leukemia cells. J Hematol Oncol. 11:112018. View Article : Google Scholar : PubMed/NCBI | |
|
Marlein CR, Piddock RE, Mistry JJ, Zaitseva L, Hellmich C, Horton RH, Zhou Z, Auger MJ, Bowles KM and Rushworth SA: CD38-driven mitochondrial trafficking promotes bioenergetic plasticity in multiple myeloma. Cancer Res. 79:2285–2297. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Dovmark TH, Saccomano M, Hulikova A, Alves F and Swietach P: Connexin-43 channels are a pathway for discharging lactate from glycolytic pancreatic ductal adenocarcinoma cells. Oncogene. 36:4538–4550. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Yu Z, Pestell TG, Lisanti MP and Pestell RG: Cancer stem cells. Int J Biochem Cell Biol. 44:2144–2151. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Mummery CL, van de Stolpe A, Roelen B and Clevers H: Chapter 12-Cancer stem cells: Where do they come from and where are they going? Stem Cells. 3rd. Mummery CL, van de Stolpe A, Roelen B and Clevers HB: Academic Press; Boston: pp. 299–328. 2021, View Article : Google Scholar | |
|
Nguyen LV, Vanner R, Dirks P and Eaves CJ: Cancer stem cells: An evolving concept. Nat Rev Cancer. 12:133–143. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF and Simeone DM: Identification of pancreatic cancer stem cells. Cancer Res. 67:1030–1038. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Gzil A, Zarębska I, Bursiewicz W, Antosik P, Grzanka D and Szylberg Ł: Markers of pancreatic cancer stem cells and their clinical and therapeutic implications. Mol Biol Rep. 46:6629–6645. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, Bruns CJ and Heeschen C: Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell. 1:313–323. 2007. View Article : Google Scholar | |
|
Rasheed ZA, Yang J, Wang Q, Kowalski J, Freed I, Murter C, Hong SM, Koorstra JB, Rajeshkumar NV, He X, et al: Prognostic significance of tumorigenic cells with mesenchymal features in pancreatic adenocarcinoma. J Natl Cancer Inst. 102:340–351. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Li C, Wu JJ, Hynes M, Dosch J, Sarkar B, Welling TH, Pasca di Magliano M and Simeone DM: c-Met is a marker of pancreatic cancer stem cells and therapeutic target. Gastroenterology. 141:2218–2227.e5. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Miranda-Lorenzo I, Dorado J, Lonardo E, Alcala S, Serrano AG, Clausell-Tormos J, Cioffi M, Megias D, Zagorac S, Balic A, et al: Intracellular autofluorescence: A biomarker for epithelial cancer stem cells. Nat Methods. 11:1161–1169. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Sancho P, Alcala S, Usachov V, Hermann PC and Sainz B Jr: The ever-changing landscape of pancreatic cancer stem cells. Pancreatology. 16:489–496. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Depeint F, Bruce WR, Shangari N, Mehta R and O'Brien PJ: Mitochondrial function and toxicity: Role of the B vitamin family on mitochondrial energy metabolism. Chem Biol Interact. 163:94–112. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Rovira M, Scott SG, Liss AS, Jensen J, Thayer SP and Leach SD: Isolation and characterization of centroacinar/terminal ductal progenitor cells in adult mouse pancreas. Proc Natl Acad Sci USA. 107:75–80. 2010. View Article : Google Scholar : | |
|
Sainz BJ Jr, Alcala S, Garcia E, Sanchez-Ripoll Y, Azevedo MM, Cioffi M, Tatari M, Miranda-Lorenzo I, Hidalgo M, Gomez-Lopez G, et al: Microenvironmental hCAP-18/LL-37 promotes pancreatic ductal adenocarcinoma by activating its cancer stem cell compartment. Gut. 64:1921–1935. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Sainz B Jr, Martín B, Tatari M, Heeschen C and Guerra S: ISG15 is a critical microenvironmental factor for pancreatic cancer stem cells. Cancer Res. 74:7309–7320. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Rausch V, Liu L, Apel A, Rettig T, Gladkich J, Labsch S, Kallifatidis G, Kaczorowski A, Groth A, Gross W, et al: Autophagy mediates survival of pancreatic tumour-initiating cells in a hypoxic microenvironment. J Pathol. 227:325–335. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Zhu H, Wang D, Zhang L, Xie X, Wu Y, Liu Y, Shao G and Su Z: Upregulation of autophagy by hypoxia-inducible factor-1α promotes EMT and metastatic ability of CD133+ pancreatic cancer stem-like cells during intermittent hypoxia. Oncol Rep. 32:935–942. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Jagust P, Alcalá S, Sainz B Jr, Heeschen C and Sancho P: Glutathione metabolism is essential for self-renewal and chemoresistance of pancreatic cancer stem cells. World J Stem Cells. 12:1410–1428. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Li D, Fu Z, Chen R, Zhao X, Zhou Y, Zeng B, Yu M, Zhou Q, Lin Q, Gao W, et al: Inhibition of glutamine metabolism counteracts pancreatic cancer stem cell features and sensitizes cells to radiotherapy. Oncotarget. 6:31151–31163. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Brandi J, Dando I, Pozza ED, Biondani G, Jenkins R, Elliott V, Park K, Fanelli G, Zolla L, Costello E, et al: Proteomic analysis of pancreatic cancer stem cells: Functional role of fatty acid synthesis and mevalonate pathways. J Proteomics. 150:310–322. 2017. View Article : Google Scholar | |
|
McDonald OG, Li X, Saunders T, Tryggvadottir R, Mentch SJ, Warmoes MO, Word AE, Carrer A, Salz TH, Natsume S, et al: Epigenomic reprogramming during pancreatic cancer progression links anabolic glucose metabolism to distant metastasis. Nat Genet. 49:367–376. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Alcalá S, Sancho P, Martinelli P, Navarro D, Pedrero C, Martín-Hijano L, Valle S, Earl J, Rodríguez-Serrano M, Ruiz-Cañas L, et al: ISG15 and ISGylation is required for pancreatic cancer stem cell mitophagy and metabolic plasticity. Nat Commun. 11:26822020. View Article : Google Scholar : PubMed/NCBI | |
|
Nimmakayala RK, Leon F, Rachagani S, Rauth S, Nallasamy P, Marimuthu S, Shailendra GK, Chhonker YS, Chugh S, Chirravuri R, et al: Metabolic programming of distinct cancer stem cells promotes metastasis of pancreatic ductal adenocarcinoma. Oncogene. 40:215–231. 2021. View Article : Google Scholar | |
|
Alistar A, Morris BB, Desnoyer R, Klepin HD, Hosseinzadeh K, Clark C, Cameron A, Leyendecker J, D'Agostino R Jr, Topaloglu U, et al: Safety and tolerability of the first-in-class agent CPI-613 in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer: A single-centre, open-label, dose-escalation, phase 1 trial. Lancet Oncol. 18:770–778. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Philip PA, Buyse ME, Alistar AT, Rocha Lima CM, Luther S, Pardee TS and Van Cutsem E: A phase III open-label trial to evaluate efficacy and safety of CPI-613 plus modified FOLFIRINOX (mFFX) versus FOLFIRINOX (FFX) in patients with metastatic adenocarcinoma of the pancreas. Future Oncol. 15:3189–3196. 2019. View Article : Google Scholar : PubMed/NCBI |
