The mTORC2 Component Rictor Contributes to Cisplatin Resistance in Human Ovarian Cancer Cells

PLoS ONE

Volumn 8, Issue 9, 2013, Pages

  Im aram, Akechai ^a   Farrand, Lee ^a   Bae, Seung Min ^a   Song, Gwonhwa ^a   Song, Yong Sang ^a   Han, Jae Yong ^a   Tsang, Benjamin K ^a,b,c  

^a Seoul National University   (South Korea)

^b UNIVERSITY OF OTTAWA   (Canada)

^c OTTAWA HOSPITAL RESEARCH INSTITUTE   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

CASPASE 3; CISPLATIN; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; PROTEIN KINASE B; PROTEIN P53; RICTOR; UNCLASSIFIED DRUG;

APOPTOSIS; ARTICLE; CANCER CELL; CONTROLLED STUDY; DOWN REGULATION; DRUG RESISTANCE; DRUG SENSITIVITY; DRUG SENSITIZATION; FEMALE; HUMAN; HUMAN CELL; OVARY CANCER; PROTEIN CLEAVAGE; PROTEIN DEGRADATION;

ANALYSIS OF VARIANCE; ANTINEOPLASTIC AGENTS; APOPTOSIS; BLOTTING, WESTERN; CARRIER PROTEINS; CASPASE 3; CISPLATIN; DRUG RESISTANCE, NEOPLASM; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; OVARIAN NEOPLASMS; RNA, SMALL INTERFERING; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84884522739     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0075455     Document Type: Article

References (44)

1. Guppy AE, Nathan PD, Rustin GJS, (2005) Epithelial Ovarian Cancer: A Review of Current Management. Clin Oncol 17: 399-411. doi:10.1016/j.clon.2005.05.009. PubMed: 16149282.
2. Kartalou M, Essigmann JM, (2001) Mechanisms of resistance to cisplatin. Mutat Res 478: 23-43. doi:10.1016/S0027-5107(01)00141-5. PubMed: 11406167.
3. Hanahan D, Weinberg RA, (2011) Hallmarks of Cancer: The Next Generation. Cell 144: 646-674. doi:10.1016/j.cell.2011.02.013. PubMed: 21376230.
4. Hsu PP, Sabatini DM, (2008) Cancer Cell Metabolism: Warburg and Beyond. Cell 134: 703-707. doi:10.1016/j.cell.2008.08.021. PubMed: 18775299.
5. Perego P, Gatti L, Righetti SC, Beretta GL, Carenini N, et al. (2003) Development of resistance to a trinuclear platinum complex in ovarian carcinoma cells. Int J Cancer 105: 617-624. doi:10.1002/ijc.11140. PubMed: 12740909.
6. Sasaki H, Sheng Y, Kotsuji F, Tsang BK, (2000) Down-regulation of X-linked inhibitor of apoptosis protein induces apoptosis in chemoresistant human ovarian cancer cells. Cancer Res 60: 5659-5666. PubMed: 11059757.
7. Fraser M, Leung BM, Yan X, Dan HC, Cheng JQ, et al. (2003) p53 Is a Determinant of X-Linked Inhibitor of Apoptosis Protein/Akt-Mediated Chemoresistance in Human Ovarian Cancer Cells. Cancer Res 63: 7081-7088. PubMed: 14612499.
8. Fraser M, Bai T, Tsang BK, (2008) Akt promotes cisplatin resistance in human ovarian cancer cells through inhibition of p53 phosphorylation and nuclear function. Int J Cancer 22: 534-546. PubMed: 17918180.
9. Abedini MR, Muller EJ, Brun J, Bergeron R, Gray DA, et al. (2008) Cisplatin induces p53-dependent FLICE-like inhibitory protein ubiquitination in ovarian cancer cells. Cancer Res 68: 4511-4517. doi:10.1158/0008-5472.CAN-08-0673. PubMed: 18559494.
10. Altomare DA, Wang HQ, Skele KL, De Rienzo A, Klein-Szanto AJ, et al. (2004) AKT and mTOR phosphorylation is frequently detected in ovarian cancer and can be targeted to disrupt ovarian tumor cell growth. Oncogene 23: 5853-5857. doi:10.1038/sj.onc.1207721. PubMed: 15208673.
11. Jiang BH, Liu LZ, (2008) Role of mTOR in anticancer drug resistance: Perspectives for improved drug treatment. Drug Resist Updates 11: 63-76. doi:10.1016/j.drup.2008.03.001. PubMed: 18440854.
12. Zhang HY, Zhang PN, Sun H, (2009) Aberration of the PI3K/AKT/mTOR signaling in epithelial ovarian cancer and its implication in cisplatin-based chemotherapy. Eur J Obstet Gyn R B 146: 81-86. PubMed: 19540648.
13. Peng DJ, Wang J, Zhou JY, Wu GS, (2010) Role of the Akt/mTOR survival pathway in cisplatin resistance in ovarian cancer cells 394. Biochem Bioph Res Co. pp.: 600-605. PubMed: 20214883.
14. No JH, Jeon YT, Park IA, Kim YB, Kim JW, et al. (2011) Activation of mTOR signaling pathway associated with adverse prognostic factors of epithelial ovarian cancer. Gynecol Oncol 121: 8-12. doi:10.1016/j.ygyno.2010.12.364. PubMed: 21276607.
15. Sparks CA, Guertin DA, (2010) Targeting mTOR: prospects for mTOR complex 2 inhibitors in cancer therapy. Oncogene 29: 3733-3744. doi:10.1038/onc.2010.139. PubMed: 20418915.
16. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM, (2005) Phosphorylation and Regulation of Akt/PKB by the Rictor-mTOR Complex. Science 307: 1098-1101. doi:10.1126/science.1106148. PubMed: 15718470.
17. Bhaskar PT, Hay N, (2007) The Two TORCs and Akt. Dev Cell 12: 487-502. doi:10.1016/j.devcel.2007.03.020. PubMed: 17419990.
18. Wu YT, Ouyang W, Lazorchak AS, Liu D, Shen HM, et al. (2011) mTOR Complex 2 Targets Akt for Proteasomal Degradation via Phosphorylation at the Hydrophobic Motif. J Biol Chem 286: 14190-14198. doi:10.1074/jbc.M111.219923. PubMed: 21321111.
19. Dan HC, Sun M, Kaneko S, Feldman RI, Nicosia SV, et al. (2004) Akt Phosphorylation and Stabilization of X-linked Inhibitor of Apoptosis Protein (XIAP). J Biol Chem 279: 5405-5412. PubMed: 14645242.
20. Abedini MR, Muller EJ, Bergeron R, Gray DA, Tsang BK, (2010) Akt promotes chemoresistance in human ovarian cancer cells by modulating cisplatin-induced, p53-dependent ubiquitination of FLICE-like inhibitory protein. Oncogene 29: 11-25. doi:10.1038/onc.2009.300. PubMed: 19802016.
21. Yang X, Fraser M, Moll UM, Basak A, Tsang BK, (2006) Akt-mediated cisplatin resistance in ovarian cancer: modulation of p53 action on caspase-dependent mitochondrial death pathway. Cancer Res 66: 3126-3136. doi:10.1158/0008-5472.CAN-05-0425. PubMed: 16540663.
22. Yang X, Fraser M, Abedini MR, Bai T, Tsang BK, (2008) Regulation of apoptosis-inducing factor-mediated, cisplatin-induced apoptosis by Akt. Br J Cancer 98: 803-808. doi:10.1038/sj.bjc.6604223. PubMed: 18283299.
23. Woo MG, Xue K, Liu J, McBride H, Tsang BK, (2012) Calpain-mediated Processing of p53-associated Parkin-like Cytoplasmic Protein (PARC) Affects Chemosensitivity of Human Ovarian Cancer Cells by Promoting p53 Subcellular Trafficking. J Biol Chem 287: 3963-3975. doi:10.1074/jbc.M111.314765. PubMed: 22117079.
24. Sarbassov DD, Ali SM, Kim DH, Guertin DA, Latek RR, et al. (2004) Rictor, a Novel Binding Partner of mTOR, Defines a Rapamycin-Insensitive and Raptor-Independent Pathway that Regulates the Cytoskeleton. Curr Biol 14: 1296-1302. doi:10.1016/j.cub.2004.06.054. PubMed: 15268862.
25. Masri J, Bernath A, Martin J, Jo OD, Vartanian R, et al. (2007) mTORC2 Activity Is Elevated in Gliomas and Promotes Growth and Cell Motility via Overexpression of Rictor. Cancer Res 67: 11712-11720. doi:10.1158/0008-5472.CAN-07-2223. PubMed: 18089801.
26. Fu L, Kim YA, Wang X, Wu X, Yue P, et al. (2009) Perifosine Inhibits Mammalian Target of Rapamycin Signaling through Facilitating Degradation of Major Components in the mTOR Axis and Induces Autophagy. Cancer Res 69: 8967-8976. doi:10.1158/0008-5472.CAN-09-2190. PubMed: 19920197.
27. Roulin D, Cerantola Y, Dormond-Meuwly A, Demartines N, Dormond O, (2010) Targeting mTORC2 inhibits colon cancer cell proliferation in vitro and tumor formation in vivo. Mol Cancer 9: 1-4. doi: 10.1186/1476-4598-9-57. PubMed: 20226010.
28. Back JH, Zhu Y, Calabro A, Queenan C, Kim AS, et al. (2012) Resveratrol-Mediated Downregulation of Rictor Attenuates Autophagic Process and Suppresses UV-Induced Skin Carcinogenesis. Photochem Photobiol 88: 1165-1172. doi:10.1111/j.1751-1097.2012.01097.x. PubMed: 22272775.
29. McDonald PC, Oloumi A, Mills J, Dobreva I, Maidan M, et al. (2008) Rictor and Integrin-Linked Kinase Interact and Regulate Akt Phosphorylation and Cancer Cell Survival. Cancer Res 68: 1618-1624. doi:10.1158/0008-5472.CAN-07-5869. PubMed: 18339839.
30. Zhang F, Zhang X, Li M, Chen P, Zhang B, et al. (2010) mTOR Complex Component Rictor Interacts with PKCζ and Regulates Cancer Cell Metastasis. Cancer Res 70: 9360-9370. doi:10.1158/0008-5472.CAN-10-0207. PubMed: 20978191.
31. Guertin DA, Stevens DM, Saitoh M, Kinkel S, Crosby K, et al. (2009) mTOR Complex 2 Is Required for the Development of Prostate Cancer Induced by Pten Loss in Mice. Cancer Cell 15: 148-159. doi:10.1016/j.ccr.2008.12.017. PubMed: 19185849.
32. Hietakangas V, Cohen SM, (2008) TOR complex 2 is needed for cell cycle progression and anchorage-independent growth of MCF7 and PC3 tumor cells. BCM Cancer 8: 1-8. PubMed: 18831768.
33. Li H, Lin J, Wang X, Yoa G, Wang L, et al. (2012) Targeting of mTORC2 prevents call migration and promotes apoptosis in breast cancer. Breast Cancer Res. Tr 2: 1-10.
34. Honda R, Tanaka H, Yasuda H, (1997) Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett 420: 25-27. doi:10.1016/S0014-5793(97)01480-4. PubMed: 9450543.
35. Moll UM, Petrenko O, (2003) The MDM2-p53 Interaction. Mol Cancer Res 1: 1001-1008. PubMed: 14707283.
36. Ali AY, Abedini MR, Tsang BK, (2011) The oncogenic phosphatase PPM1D confers cisplatin resistance in ovarian carcinoma cells by attenuating checkpoint kinase 1 and p53 activation. Oncogene 29: 1-12. PubMed: 21927021.
37. Fraser M, Chan SL, Chan SSL, Fiscus RR, Tsang BK, (2006) Regulation of p53 and suppression of apoptosis by the soluble guanylyl cyclase/cGMP pathway in human ovarian cancer cells. Oncogene 25: 2203-2212. doi:10.1038/sj.onc.1209251. PubMed: 16288207.
38. Feng Z, Zhang H, Levine AJ, Jin S, (2005) The coordinate regulation of the p53 and mTOR pathways in cells. Proc Natl Acad Sci U S A 102: 8204-8209. doi:10.1073/pnas.0502857102. PubMed: 15928081.
39. Shaw TJ, Senterman MK, Dawson K, Crane CA, Vanderhyden BC, (2004) Characterization of intraperitoneal, orthotopic, and metastatic xenograft models of human ovarian cancer. Mol Ther 10: 1032-1042. doi:10.1016/j.ymthe.2004.08.013. PubMed: 15564135.
40. Abedini MR, Qiu Q, Yan X, Tsang BK, (2004) Possible role of FLICE-like inhibitory protein (FLIP) in chemoresistant ovarian cancer cells in vitro. Oncogene 23: 6997-7004. doi:10.1038/sj.onc.1207925. PubMed: 15258564.
41. Schuijer M, Berns EMJJ, (2003) TP53 and Cancer. Hum Mutat 21: 285-291. doi:10.1002/humu.10181. PubMed: 12619114.
42. Kmet LM, Cook LS, Magliocco AM, (2003) A Review of p53 Expression and Mutation in Human Benign, Low Malignant Potential, and Invasive Epithelial Ovarian Tumors. Cancer 97: 389-404. doi:10.1002/cncr.11064. PubMed: 12518363.
43. Ikenoue T, Inoki K, Yang Q, Zhou X, Guan KL, (2008) Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signaling. EMBO J 27: 1919-1931. doi:10.1038/emboj.2008.119. PubMed: 18566587.
44. Facchinetti V, Ouyang W, Wei H, Soto N, Lazorchak A, et al. (2008) The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C. EMBO J 27: 1932-1943. doi:10.1038/emboj.2008.120. PubMed: 18566586.