Regulation of autophagy and EMT by the interplay between p53 and RAS during cancer progression (Review)
- Authors:
- Xiaofei Zhang
- Qian Cheng
- Huijing Yin
- Gong Yang
-
Affiliations: Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China, Department of Orthopedics, the Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China - Published online on: May 31, 2017 https://doi.org/10.3892/ijo.2017.4025
- Pages: 18-24
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Stępiński D: Nucleolus-derived mediators in oncogenic stress response and activation of p53-dependent pathways. Histochem Cell Biol. 146:119–139. 2016. View Article : Google Scholar | |
|
Merino D and Malkin D: p53 and hereditary cancer. Subcell Biochem. 85:1–16. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Muller PA and Vousden KH: p53 mutations in cancer. Nat Cell Biol. 15:2–8. 2013. View Article : Google Scholar | |
|
Freed-Pastor WA and Prives C: Mutant p53: One name, many proteins. Genes Dev. 26:1268–1286. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Silva JL, De Moura Gallo CV, Costa DC and Rangel LP: Prion-like aggregation of mutant p53 in cancer. Trends Biochem Sci. 39:260–267. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Fang B: RAS signaling and anti-RAS therapy: Lessons learned from genetically engineered mouse models, human cancer cells, and patient-related studies. Acta Biochim Biophys Sin (Shanghai). 48:27–38. 2016. | |
|
Kimmelman AC: Metabolic dependencies in RAS-driven cancers. Clin Cancer Res. 21:1828–1834. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Stites EC and Ravichandran KS: A systems perspective of ras signaling in cancer. Clin Cancer Res. 15(5): 1510–1513. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Vandal G, Geiling B and Dankort D: Ras effector mutant expression suggest a negative regulator inhibits lung tumor formation. PLoS One. 9:e847452014. View Article : Google Scholar : PubMed/NCBI | |
|
Xia M and Land H: Tumor suppressor p53 restricts Ras stimulation of RhoA and cancer cell motility. Nat Struct Mol Biol. 14:215–223. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Meylan E, Dooley AL, Feldser DM, Shen L, Turk E, Ouyang C and Jacks T: Requirement for NF-kappaB signalling in a mouse model of lung adenocarcinoma. Nature. 462:104–107. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Boiko AD, Porteous S, Razorenova OV, Krivokrysenko VI, Williams BR and Gudkov AV: A systematic search for downstream mediators of tumor suppressor function of p53 reveals a major role of BTG2 in suppression of Ras-induced transformation. Genes Dev. 20:236–252. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Song H, Hollstein M and Xu Y: p53 gain-of-function cancer mutants induce genetic instability by inactivating ATM. Nat Cell Biol. 9:573–580. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Lorin S, Hamaï A, Mehrpour M and Codogno P: Autophagy regulation and its role in cancer. Semin Cancer Biol. 23:361–379. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Mizushima N, Levine B, Cuervo AM and Klionsky DJ: Autophagy fights disease through cellular self-digestion. Nature. 451:1069–1075. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Kumar A, Singh UK and Chaudhary A: Targeting autophagy to overcome drug resistance in cancer therapy. Future Med Chem. 7:1535–1542. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
White E and DiPaola RS: The double-edged sword of autophagy modulation in cancer. Clin Cancer Res. 15:5308–53016. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Tang J, Di J, Cao H, Bai J and Zheng J: p53-mediated autophagic regulation: A prospective strategy for cancer therapy. Cancer Lett. 363:101–107. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Tasdemir E, Maiuri MC, Galluzzi L, Vitale I, Djavaheri-Mergny M, D'Amelio M, Criollo A, Morselli E, Zhu C, Harper F, et al: Regulation of autophagy by cytoplasmic p53. Nat Cell Biol. 10:676–687. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Schmukler E, Kloog Y and Pinkas-Kramarski R: Ras and autophagy in cancer development and therapy. Oncotarget. 5:577–586. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Lock R, Kenific CM, Leidal AM, Salas E and Debnath J: Autophagy-dependent production of secreted factors facilitates oncogenic RAS-driven invasion. Cancer Discov. 4:466–479. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
White E: Deconvoluting the context-dependent role for autophagy in cancer. Nat Rev Cancer. 12:401–410. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Budanov AV: Stress-responsive sestrins link p53 with redox regulation and mammalian target of rapamycin signaling. Antioxid Redox Signal. 15:1679–1690. 2011. View Article : Google Scholar : | |
|
Huang J and Manning BD: The TSC1–TSC2 complex: A molecular switchboard controlling cell growth. Biochem J. 412:179–190. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A, Vasquez DS, Turk BE and Shaw RJ: AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell. 30:214–226. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Kong B, Wu W, Cheng T, Schlitter AM, Qian C, Bruns P, Jian Z, Jäger C, Regel I, Raulefs S, et al: A subset of metastatic pancreatic ductal adenocarcinomas depends quantitatively on oncogenic Kras/Mek/Erk-induced hyperactive mTOR signalling. Gut. 65:647–657. 2016. View Article : Google Scholar | |
|
Kim J, Kundu M, Viollet B and Guan KL: AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 13:132–141. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Mizushima N, Yoshimori T and Ohsumi Y: The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol. 27:107–132. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Eby KG, Rosenbluth JM, Mays DJ, Marshall CB, Barton CE, Sinha S, Johnson KN, Tang L and Pietenpol JA: ISG20L1 is a p53 family target gene that modulates genotoxic stress-induced autophagy. Mol Cancer. 9:952010. View Article : Google Scholar : PubMed/NCBI | |
|
Kenzelmann Broz D, Spano Mello S, Bieging KT, Jiang D, Dusek RL, Brady CA, Sidow A and Attardi LD: Global genomic profiling reveals an extensive p53-regulated autophagy program contributing to key p53 responses. Genes Dev. 27:1016–1031. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Gao W, Shen Z, Shang L and Wang X: Upregulation of human autophagy-initiation kinase ULK1 by tumor suppressor p53 contributes to DNA-damage-induced cell death. Cell Death Differ. 18:1598–1607. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Guo JY, Karsli-Uzunbas G, Mathew R, Aisner SC, Kamphorst JJ, Strohecker AM, Chen G, Price S, Lu W, Teng X, et al: Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis. Genes Dev. 27:1447–1461. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Kim MJ, Woo SJ, Yoon CH, Lee JS, An S, Choi YH, Hwang SG, Yoon G and Lee SJ: Involvement of autophagy in oncogenic K-Ras-induced malignant cell transformation. J Biol Chem. 286:12924–12932. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Kinsey C, Balakrishnan V, O'Dell MR, Huang JL, Newman L, Whitney-Miller CL, Hezel AF and Land H: Plac8 links oncogenic mutations to regulation of autophagy and is critical to pancreatic cancer progression. Cell Rep. 7:1143–1155. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Desai S, Liu Z, Yao J, Patel N, Chen J, Wu Y, Ahn EE, Fodstad O and Tan M: Heat shock factor 1 (HSF1) controls chemoresistance and autophagy through transcriptional regulation of autophagy-related protein 7 (ATG7). J Biol Chem. 288:9165–9176. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Vydra N, Toma A and Widlak W: Pleiotropic role of HSF1 in neoplastic transformation. Curr Cancer Drug Targets. 14:144–155. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Dai C, Santagata S, Tang Z, Shi J, Cao J, Kwon H, Bronson RT, Whitesell L and Lindquist S: Loss of tumor suppressor NF1 activates HSF1 to promote carcinogenesis. J Clin Invest. 122:3742–3754. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Li Q and Martinez JD: P53 is transported into the nucleus via an Hsf1-dependent nuclear localization mechanism. Mol Carcinog. 50:143–152. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Hu YL, Jahangiri A, De Lay M and Aghi MK: Hypoxia-induced tumor cell autophagy mediates resistance to anti-angiogenic therapy. Autophagy. 8:979–981. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Chen C, Pore N, Behrooz A, Ismail-Beigi F and Maity A: Regulation of glut1 mRNA by hypoxia-inducible factor-1. Interaction between H-ras and hypoxia. J Biol Chem. 276:9519–9525. 2001. View Article : Google Scholar | |
|
Nieminen AL, Qanungo S, Schneider EA, Jiang BH and Agani FH: Mdm2 and HIF-1alpha interaction in tumor cells during hypoxia. J Cell Physiol. 204:364–369. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Robertson ED, Semenchenko K and Wasylyk B: Crosstalk between Mdm2, p53 and HIF1-α: Distinct responses to oxygen stress and implications for tumour hypoxia. Subcell Biochem. 85:199–214. 2014. View Article : Google Scholar | |
|
Hay ED: An overview of epithelio-mesenchymal transformation. Acta Anat (Basel). 154:8–20. 1995. View Article : Google Scholar | |
|
Lamouille S, Xu J and Derynck R: Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 15:178–196. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Puisieux A, Brabletz T and Caramel J: Oncogenic roles of EMT-inducing transcription factors. Nat Cell Biol. 16:488–494. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Fischer KR, Durrans A, Lee S, Sheng J, Li F, Wong ST, Choi H, El Rayes T, Ryu S, Troeger J, et al: Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. Nature. 527:472–476. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Zheng X, Carstens JL, Kim J, Scheible M, Kaye J, Sugimoto H, Wu CC, LeBleu VS and Kalluri R: Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature. 527:525–530. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Y, Ngo VN, Marani M, Yang Y, Wright G, Staudt LM and Downward J: Critical role for transcriptional repressor Snail2 in transformation by oncogenic RAS in colorectal carcinoma cells. Oncogene. 29:4658–4670. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Gonzalez DM and Medici D: Signaling mechanisms of the epithelial-mesenchymal transition. Sci Signal. 7:re82014. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang J, Lei Y, Gao X, Liang Q, Li L, Feng J, Hou P, Han L, Zhang Y, Huang B, et al: p53 Attenuates the oncogenic Ras-induced epithelial-mesenchymal transition in human mammary epithelial cells. Biochem Biophys Res Commun. 434:606–613. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Z, Wade P, Mandell KJ, Akyildiz A, Parkos CA, Mrsny RJ and Nusrat A: Raf 1 represses expression of the tight junction protein occludin via activation of the zinc-finger transcription factor slug. Oncogene. 26:1222–1230. 2007. View Article : Google Scholar | |
|
Saegusa M, Hashimura M, Kuwata T and Okayasu I: Requirement of the Akt/beta-catenin pathway for uterine carcinosarcoma genesis, modulating E-cadherin expression through the transactivation of slug. Am J Pathol. 174:2107–2115. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Wang SP, Wang WL, Chang YL, Wu CT, Chao YC, Kao SH, Yuan A, Lin CW, Yang SC, Chan WK, et al: p53 controls cancer cell invasion by inducing the MDM2-mediated degradation of Slug. Nat Cell Biol. 11:694–704. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Y, Bu F, Royer C, Serres S, Larkin JR, Soto MS, Sibson NR, Salter V, Fritzsche F, Turnquist C, et al: ASPP2 controls epithelial plasticity and inhibits metastasis through β-catenin-dependent regulation of ZEB1. Nat Cell Biol. 16:1092–1104. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Kim T, Veronese A, Pichiorri F, Lee TJ, Jeon YJ, Volinia S, Pineau P, Marchio A, Palatini J, Suh SS, et al: p53 regulates epithelial-mesenchymal transition through microRNAs targeting ZEB1 and ZEB2. J Exp Med. 208:875–883. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Chang CJ, Chao CH, Xia W, Yang JY, Xiong Y, Li CW, Yu WH, Rehman SK, Hsu JL, Lee HH, et al: p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs. Nat Cell Biol. 13:317–323. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Ansieau S, Bastid J, Doreau A, Morel AP, Bouchet BP, Thomas C, Fauvet F, Puisieux I, Doglioni C, Piccinin S, et al: Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence. Cancer Cell. 14:79–89. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Jiang Y, Xie X, Li Z, Wang Z, Zhang Y, Ling ZQ, Pan Y, Wang Z and Chen Y: Functional cooperation of RKTG with p53 in tumorigenesis and epithelial-mesenchymal transition. Cancer Res. 71:2959–2968. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Gibbons DL, Lin W, Creighton CJ, Rizvi ZH, Gregory PA, Goodall GJ, Thilaganathan N, Du L, Zhang Y, Pertsemlidis A, et al: Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression. Genes Dev. 23:2140–2151. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Roger L, Jullien L, Gire V and Roux P: Gain of oncogenic function of p53 mutants regulates E-cadherin expression uncoupled from cell invasion in colon cancer cells. J Cell Sci. 123:1295–1305. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Ohashi S, Natsuizaka M, Wong GS, Michaylira CZ, Grugan KD, Stairs DB, Kalabis J, Vega ME, Kalman RA, Nakagawa M, et al: Epidermal growth factor receptor and mutant p53 expand an esophageal cellular subpopulation capable of epithelial-to-mesenchymal transition through ZEB transcription factors. Cancer Res. 70:4174–4184. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Jiang Z, Deng T, Jones R, Li H, Herschkowitz JI, Liu JC, Weigman VJ, Tsao MS, Lane TF, Perou CM, et al: Rb deletion in mouse mammary progenitors induces luminal-B or basal-like/EMT tumor subtypes depending on p53 status. J Clin Invest. 120:3296–3309. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Okada T, Sinha S, Esposito I, Schiavon G, López-Lago MA, Su W, Pratilas CA, Abele C, Hernandez JM, Ohara M, et al: The Rho GTPase Rnd1 suppresses mammary tumorigenesis and EMT by restraining Ras-MAPK signalling. Nat Cell Biol. 17:81–94. 2015. View Article : Google Scholar | |
|
Gao T, Li JZ, Lu Y, Zhang CY, Li Q, Mao J and Li LH: The mechanism between epithelial mesenchymal transition in breast cancer and hypoxia microenvironment. Biomed Pharmacother. 80:393–405. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Imai T, Horiuchi A, Wang C, Oka K, Ohira S, Nikaido T and Konishi I: Hypoxia attenuates the expression of E-cadherin via up-regulation of SNAIL in ovarian carcinoma cells. Am J Pathol. 163:1437–1447. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang L, Huang G, Li X, Zhang Y, Jiang Y, Shen J, Liu J, Wang Q, Zhu J, Feng X, et al: Hypoxia induces epithelial-mesenchymal transition via activation of SNAI1 by hypoxia-inducible factor-1α in hepatocellular carcinoma. BMC Cancer. 13:1082013. View Article : Google Scholar | |
|
Cui Y, Li YY, Li J, Zhang HY, Wang F, Bai X and Li SS: STAT3 regulates hypoxia-induced epithelial mesenchymal transition in oesophageal squamous cell cancer. Oncol Rep. 36:108–116. 2016.PubMed/NCBI | |
|
Tsai YP and Wu KJ: Hypoxia-regulated target genes implicated in tumor metastasis. J Biomed Sci. 19:1022012. View Article : Google Scholar : PubMed/NCBI | |
|
Tsai JH and Yang J: Epithelial-mesenchymal plasticity in carcinoma metastasis. Genes Dev. 27:2192–2206. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Gugnoni M, Sancisi V, Manzotti G, Gandolfi G and Ciarrocchi A: Autophagy and epithelial-mesenchymal transition: An intricate interplay in cancer. Cell Death Dis. 7:e25202016. View Article : Google Scholar : PubMed/NCBI | |
|
Qin W, Li C, Zheng W, Guo Q, Zhang Y, Kang M, Zhang B, Yang B, Li B, Yang H, et al: Inhibition of autophagy promotes metastasis and glycolysis by inducing ROS in gastric cancer cells. Oncotarget. 6:39839–39854. 2015.PubMed/NCBI | |
|
Qiang L and He YY: Autophagy deficiency stabilizes TWIST1 to promote epithelial-mesenchymal transition. Autophagy. 10:1864–1865. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Catalano M, D'Alessandro G, Lepore F, Corazzari M, Caldarola S, Valacca C, Faienza F, Esposito V, Limatola C, Cecconi F, et al: Autophagy induction impairs migration and invasion by reversing EMT in glioblastoma cells. Mol Oncol. 9:1612–1625. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Lv Q, Hua F and Hu ZW: DEDD, a novel tumor repressor, reverses epithelial-mesenchymal transition by activating selective autophagy. Autophagy. 8:1675–1676. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Li J, Yang B, Zhou Q, Wu Y, Shang D, Guo Y, Song Z, Zheng Q and Xiong J: Autophagy promotes hepatocellular carcinoma cell invasion through activation of epithelial-mesenchymal transition. Carcinogenesis. 34:1343–1351. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Wei SC and Yang J: Forcing through tumor metastasis: The interplay between tissue rigidity and epithelial-mesenchymal transition. Trends Cell Biol. 26:111–120. 2016. View Article : Google Scholar : | |
|
Tojkander S, Gateva G and Lappalainen P: Actin stress fibers-assembly, dynamics and biological roles. J Cell Sci. 125:1855–1864. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Ni HM, Williams JA and Ding WX: Mitochondrial dynamics and mitochondrial quality control. Redox Biol. 4:6–13. 2015. View Article : Google Scholar : | |
|
Youle RJ and van der Bliek AM: Mitochondrial fission, fusion, and stress. Science. 337:1062–1065. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Zhao J, Zhang J, Yu M, Xie Y, Huang Y, Wolff DW, Abel PW and Tu Y: Mitochondrial dynamics regulates migration and invasion of breast cancer cells. Oncogene. 32:4814–4824. 2013. View Article : Google Scholar | |
|
Ketschek A and Gallo G: Nerve growth factor induces axonal filopodia through localized microdomains of phosphoinositide 3-kinase activity that drive the formation of cytoskeletal precursors to filopodia. J Neurosci. 30:12185–12197. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Parada LF, Land H, Weinberg RA, Wolf D and Rotter V: Cooperation between gene encoding p53 tumour antigen and ras in cellular transformation. Nature. 312:649–651. 1984. View Article : Google Scholar : PubMed/NCBI | |
|
Jenkins JR, Rudge K and Currie GA: Cellular immortalization by a cDNA clone encoding the transformation-associated phosphoprotein p53. Nature. 312:651–654. 1984. View Article : Google Scholar : PubMed/NCBI | |
|
Eliyahu D, Raz A, Gruss P, Givol D and Oren M: Participation of p53 cellular tumour antigen in transformation of normal embryonic cells. Nature. 312:646–649. 1984. View Article : Google Scholar : PubMed/NCBI | |
|
DuPage M, Dooley AL and Jacks T: Conditional mouse lung cancer models using adenoviral or lentiviral delivery of Cre recombinase. Nat Protoc. 4:1064–1072. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Hingorani SR, Wang L, Multani AS, Combs C, Deramaudt TB, Hruban RH, Rustgi AK, Chang S and Tuveson DA: Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell. 7:469–483. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Tsumura H, Yoshida T, Saito H, Imanaka-Yoshida K and Suzuki N: Cooperation of oncogenic K-ras and p53 deficiency in pleomorphic rhabdomyosarcoma development in adult mice. Oncogene. 25:7673–7679. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Zheng S, El-Naggar AK, Kim ES, Kurie JM and Lozano G: A genetic mouse model for metastatic lung cancer with gender differences in survival. Oncogene. 26:6896–6904. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Muñoz DM, Tung T, Agnihotri S, Singh S, Guha A, Zadeh G and Hawkins C: Loss of p53 cooperates with K-ras activation to induce glioma formation in a region-independent manner. Glia. 61:1862–1872. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Solomon H, Brosh R, Buganim Y and Rotter V: Inactivation of the p53 tumor suppressor gene and activation of the Ras oncogene: Cooperative events in tumorigenesis. Discov Med. 9:448–454. 2010.PubMed/NCBI | |
|
Jackson JG and Lozano G: The mutant p53 mouse as a preclinical model. Oncogene. 32:4325–4330. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Bertheau P, Turpin E, Rickman DS, Espié M, de Reyniès A, Feugeas JP, Plassa LF, Soliman H, Varna M, de Roquancourt A, et al: Exquisite sensitivity of TP53 mutant and basal breast cancers to a dose-dense epirubicin-cyclophosphamide regimen. PLoS Med. 4:e902007. View Article : Google Scholar : PubMed/NCBI | |
|
Cassinelli G, Zuco V, Gatti L, Lanzi C, Zaffaroni N, Colombo D and Perego P: Targeting the Akt kinase to modulate survival, invasiveness and drug resistance of cancer cells. Curr Med Chem. 20:1923–1945. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Gurpinar E and Vousden KH: Hitting cancers' weak spots: Vulnerabilities imposed by p53 mutation. Trends Cell Biol. 25:486–495. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Bournet B, Buscail C, Muscari F, Cordelier P and Buscail L: Targeting KRAS for diagnosis, prognosis, and treatment of pancreatic cancer: Hopes and realities. Eur J Cancer. 54:75–83. 2016. View Article : Google Scholar : PubMed/NCBI |
