DEPTOR promotes survival of cervical squamous cell carcinoma cells and its silencing induces apoptosis through downregulating PI3K/AKT and by up-regulating p38 MAP kinase

Oncotarget

Volumn 7, Issue 17, 2016, Pages 24154-24171

  Srinivas, Kalanghad Puthankalam ^a   Viji, Remadevi ^a   Dan, Vipin Mohan ^a   Sajitha, Indira Sukumaran ^a   Prakash, Rajappan ^a   Rahul, Puthan Valappi ^a   Santhoshkumar, Thankayyan R ^a   Lakshmi, Subhadra ^b   Pillai, Madhavan Radhakrishna ^a  

^a RAJIV GANDHI CENTRE FOR BIOTECHNOLOGY   (India)

^b REGIONAL CANCER CENTRE   (India)

Author keywords

Apoptosis; Cervical cancer; DEPTOR; ERK and p38; PI3K AKT

Indexed keywords

CASPASE 9; ENDOTHELIAL NITRIC OXIDE SYNTHASE; INDUCIBLE NITRIC OXIDE SYNTHASE; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; MITOGEN ACTIVATED PROTEIN KINASE P38; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN E6; PROTEIN E7; PROTEIN KINASE B; PROTEIN P53; PUMA PROTEIN; S6 KINASE; DEPTOR PROTEIN, HUMAN; SIGNAL PEPTIDE; TUMOR MARKER;

APOPTOSIS; ARTICLE; CANCER CELL LINE; CANCER SURVIVAL; CANCER TISSUE; CELL DEATH; CONTROLLED STUDY; DEPTOR GENE; DOWN REGULATION; ECTOPIC EXPRESSION; ENZYME ACTIVATION; ENZYME INHIBITION; FEMALE; GENE OVEREXPRESSION; GENE SILENCING; HUMAN; HUMAN TISSUE; ME 180 CELL LINE; NEGATIVE FEEDBACK; ONCOGENE; PROTEIN INDUCTION; REGULATORY MECHANISM; SIGNAL TRANSDUCTION; SIHA CELL LINE; SQUAMOUS CELL CARCINOMA CELL LINE; UPREGULATION; UTERINE CERVIX CARCINOMA; CELL PROLIFERATION; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; PATHOLOGY; PROGNOSIS; SQUAMOUS CELL CARCINOMA; TUMOR CELL CULTURE; UTERINE CERVIX TUMOR;

APOPTOSIS; BIOMARKERS, TUMOR; CARCINOMA, SQUAMOUS CELL; CELL PROLIFERATION; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; P38 MITOGEN-ACTIVATED PROTEIN KINASES; PHOSPHATIDYLINOSITOL 3-KINASES; PROGNOSIS; PROTO-ONCOGENE PROTEINS C-AKT; TUMOR CELLS, CULTURED; UTERINE CERVICAL NEOPLASMS;

EID: 84966628827     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.8131     Document Type: Article

References (66)

1. Sarbassov D, Ali SM, Sabatini DM. Growing roles for mTOR pathway. Current Opinion in Cell Biology. 2005; 17: 596-603.
2. Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell 2007; 12: 9-22.
3. Duran RV, Hall MN. Regulation of TOR by small GTPases. EMBO reports. 2012; 13:121-128.
4. Peterson TR, Laplante M, Thoreen CC, Sancak Y, Kang SA, Kuehl WM, Gray NS, Sabatini DM. DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival. Cell. 2009; 137: 873-886.
5. Duan S, Skaar JR, Kuchay S, Toschi A, Kanarek N, Ben-Neriah Y, Pagano M. mTOR generates an autoamplification loop by triggering the βTrCP and CK1a-dependent degradation of DEPTOR. Molecular Cell. 2011; 44: 317-324.
6. Li H, Sun GY, Zhao Y, Thomas D, Greenson JK, Zalupski MM, Ben-Josef E, Sun Y. DEPTOR has growth suppression activity against pancreatic cancer cells. Oncotarget. 2014; 5:12811-12819. doi: 10.18632/oncotarget.2659.
7. Wang Z, Zhong J, Inuzuka H, Gao D, Shaik S, Sarkar FH, Wei W. An evolving role for DEPTOR in tumor development and progression. Neoplasia. 2012; 14:368-375.
8. Zhao Y, Sun Y. Targeting the mTOR-DEPTOR pathway by CRL E3 ubiquitin ligases: therapeutic application. Neoplasia. 2012; 14: 360-367.
9. Foster H, Coley HM, Goumenou A, Pados G, Harvey A, Karteris E. Differential expression of mTOR signalling components in drug resistance in ovarian cancer. Anticancer Research. 2010; 30: 3529-3534.
10. Pei L, Xie P, Zhou E, Yang Q, Luo Y, Tang Z. Overexpression of DEP domain containing mTORinteracting protein correlates with poor prognosis in differentiated thyroid carcinoma. Molecular Medicine Reports 2011; 4: 817-823.
11. Yen CH, Lu YC, Li CH, Lee CM, Chen CY, Cheng MY, Huang SF, Chen KF, Cheng AL, Liao LY, Lee YHW, Chen YMA. Functional characterization of Glycine N-Methyltransferase and its interactive protein DEPDC6/ DEPTOR in Hepatocellular carcinoma. Molecular Medicine. 2012; 18: 286-296.
12. Zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical implication. Nature Reviews Cancer. 2002; 2: 342-350.
13. Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S. Human papillomavirus and cervical cancer. Lancet. 2007; 370:890-907.
14. Howie HL, Katzenellenbogen RA, Galloway DA. Papillomavirus E6 proteins. Virology. 2009; 384:324-334.
15. Spangle JM, Munger K. The Human Papillomavirus Type 16 E6 oncoprotein activates mTORC1 signaling and increases protein synthesis. Journal of Virology. 2010; 84: 9398-9407.
16. Accardi R, Rubino R, Scalise M, Gheit T, Shahzad N, Thomas M, Banks L, Indiveri C, Sylla BS, Cardone RA, Reshkin SJ, Tommasino M. E6 and E7 from Human Papillomavirus type 16 co-operate to target the PDZ protein Na/H exchange regulatory factor 1. Journal of Virology. 2011; 85: 8208-8216.
17. Surviladze Z, Sterk RT, DeHaro SA, Ozbun MA. Cellular Entry of Human Papillomavirus Type 16 Involves Activation of the Phosphatidylinositol 3-Kinase/Akt/mTOR Pathway and Inhibition of Autophagy. Journal of Virology. 2013; 87: 2508-2517.
18. Menges CW, Baglia LA, Lapoint R, McCance DJ. Human papillomavirus type 16 E7 up-regulates AKT activity through the retinoblastoma protein. Cancer Research. 2006; 66:5555-5559.
19. Charette ST, McCance DJ. The E7 protein from human papillomavirus type 16 enhances keratinocyte migration in an Akt-dependent manner. Oncogene. 2007; 26:7386-7390.
20. Shim C, Zhang W, Rhee CH, Lee JH. Profiling of differentially expressed genes in human primary cervical cancer by complementary DNA expression array. Clinical Cancer Research. 1998; 4:3045-50.
21. Lai CH, Hsueh S, Hong JH, Chang TC, Tseng CJ, Chou HH, Huang KG, Lin JD. Are adenocarcinomas and adenosquamous carcinomas different from squamous carcinomas in stage IB and II cervical cancer patients undergoing primary radical surgery?. International Journal of Gynecological Cancer. 1999; 9: 28-36.
22. Contag SA, Gostout BS, Clayton AC, Dixon MH, McGovern RM, Calhoun ES. Comparison of gene expression in squamous cell carcinoma and adenocarcinoma of the uterine cervix. Gynecologic Oncology. 2004; 95: 610-7.
23. Danial NN, Korsmeyer SJ. Cell death: critical control points. Cell 2004; 116: 205-219.
24. Taylor RC, Cullen SP, Martin SJ. Apoptosis: Controlled demolition at the cellular level. Nature Reviews Molecular Cell Biology. 2008; 9:231-241.
25. Sobhan PK, Seervi M, Deb L, Varghese S, Soman A, Joseph J, Mathew KA, Raghu G, Thomas G, Sreekumar E, Manjula S, Santosh Kumar T. R. Calpain and reactive oxygen species targets Bax for mitochondrial mermeabilisation and caspase activation in zerumbone induced apoptosis. Plos one. 2013; 8: 1-13.
26. Goodwin EC, DiMaio D. Repression of human papillomavirus oncogenes in HeLa cervical carcinoma cells causes the orderly reactivation of dormant tumor suppressor pathways. Proceedings of National Academy of Sciences USA. 2000; 97: 12513-12518.
27. Nakano K, Vousden KH. PUMA, a novel proapoptotic gene, is induced by p53. Molecular Cell. 2001; 7: 683-94.
28. Ji H, Ding Z, Hawke D, Xing D, Jiang BH, Mills GB, Lu Z. AKT-dependent phosphorylation of Niban regulates nucleophosmin-and MDM2-mediated p53 stability and cell apoptosis. EMBO reports. 2012; 13: 554-560.
29. Xu W, Liu LZ, Loizidou M, Ahmed M, Charles IG. The role of nitric oxide in cancer. Cell Research. 2002; 12:311-320.
30. Fulton D, Gratton JP, McCabe TJ, Fontana J, Fujio Y, Walsh K, Franke TF, Papapetropoulos A, Sessa WC. Regulation of endothelium derived nitric oxide production by the protein kinase Akt. Nature. 1999; 399: 597-601.
31. Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R, Zeiher AM. Activation of nitric oxide synthase in endothelial cells byAkt-dependent phosphorylation. Nature. 1999; 399: 601-605.
32. Lakshmikanthan S, Zheng X, Nishijima Y, Sobczak M, Szabo A, Vasquez-Vivar J, Zhang DX, Chrzanowska-Wodnicka M. Rap1 promotes endothelial mechanosensing complex formation, NO release and normal endothelial function. EMBO reports. 2015; 16:628-637.
33. Soliman GA, Acosta-Jaquez HA, Dunlop EA, Ekim B, Maj NE, Tee AR, Fingar DC. mTOR Ser-2481 autophosphorylation monitors mTORC-specific catalytic activity and clarifies rapamycin mechanism of action. Journal of Biological Chemistry. 2010; 285: 7866-7879.
34. Mayo LD, Donner DB. A phosphatidylinositol 3-kinaseyAkt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus. Proceedings of National Academy of Sciences USA. 2001; 98: 11598-11603.
35. Phung TL, Ziv K, Dabydeen D, Eyiah-Mensah G, Riveros M, Perruzzi C, Sun J, Monahan-earley RA, Shiojina I, Nagy JA, Lin MI, Walsh K, Dvorak AM, Briscoe DM, Neeman M, Sessa WC, Dvorak HF, Benjamin LE. Pathological angiogenesis is induced by sustained Akt signaling and inhibited by rapamycin. Cancer Cell. 2006; 10: 159-170.
36. Rudelius M, Pittaluga S, Nishizuka S, Pham Th, Fend F, Jaffe ES, Quintanilla-Martinez L, Raffeld M. Constitutive activation of Akt contributes to the pathogenesis and survival of mantle cell lymphoma. Blood. 2006; 108: 1668-1676.
37. Sun, X. J., P. Rothenberg, C. R. Kahn, J. M. Backer, E. Araki, P. A. Wilden, D. A. Cahill, B. J. Goldstein, M. F. White. Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein. Nature. 1991; 352:73-77.
38. Uddin, S., B. Majchrzak, P. C. Wang, S. Modi, M. K. Khan, E. N. Fish, L. C. Platanias. Interferon-dependent activation of the serine kinase PI 39-kinase requires engagement of the IRS pathway but not the Stat pathway. Biochemical and Biophysical Research Communications. 2000; 270:158-162.
39. Shaw LM. Identification of Insulin Receptor Substrate 1 (IRS-1) and IRS-2 as signaling intermediates in the a6b4 Integrin-dependent activation of Phosphoinositide 3-OH Kinase and promotion of invasion. Molecular and Cellular Biology. 2001; 21: 5082-5093.
40. Um SH, Frigerio F, Watanabe M, Picard F, Joaquin M, Sticker M, Fumagalli S, Allegrini PR, Kozma SC, Auwerx J, Thomas G. Absence of S6K1 protects against age-and diet-induced obesity while enhancing insulin sensitivity. Nature. 2004; 431: 200-205.
41. Tremblay F, Bru le S, Hee Um S, Li Y, Masuda K, Roden M, Jian Sun X, Krebs M, Polakiewicz RD, Thomas G, Marette A. Identification of IRS-1 Ser-1101 as a target of S6K1 in nutrient-and obesity-induced insulin resistance. PNAS. 2007; 104: 14056-14061.
42. Mendonza MC, Emrah Er E, Blenis J. The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation. Trends in Biochemical Sciences. 2011; 36: 320-328.
43. Wada T, Penninger JM. Mitogen-activated protein kinases in apoptosis regulation. Oncogene. 2004; 23: 2838-2849.
44. Chang L, Karin M. Mammalian MAP kinase signalling cascades. Nature. 2001; 410: 37-40.
45. Liu B, Fang M, Lu Y, Lu Y, Mills GB, Fan Z. Involvement of JNK-mediated pathway in EGF-mediated protection against paclitaxel-induced apoptosis in SiHa human cervical cancer cells. British Journal of Cancer. 2001; 85: 303-11.
46. Perfettini JL, Castedo M, Nardacci R, Ciccosanti F, Boya P, Roumier T, Larochette N, Piacentini M, Kroemer G. Essential role of p53 phosphorylation by p38 MAPK in apoptosis induction by the HIV-1 envelope. Journal of Experimental Medicine. 2005; 201: 279-289.
47. Taylor CA, Zheng Q, Liu Z, Thompson JE. Role of p38 and JNK MAPK signaling pathways and tumor suppressor p53 on induction of apoptosis in response to Ad-eIF5A1 in A549 lung cancer cells. Molecular Cancer. 2013; 12: 1-11.
48. Czabotar PE, Lessene G, Strasser A, Adams JM. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nature Reviews Molecular Cell Biology. 2014; 15: 49-63.
49. Carrasco DR, Tonon G, Huang Y, Zhang Y, Sinha R, Feng B, Stewart JP, Zhan F, Khatry D, Protopopova M, Protopopov A, Sukhdeo K, Hanamura I, Stephens O, Barlogie B, Anderson KC, Chin L, Shaughnessy JD Jr, Brennan C, DePinho RA. High-resolution genomic profiles define distinct clinicopathogenetic subgroups of multiple myeloma patients. Cancer Cell. 2006; 9:313-325.
50. Zhao Y, Xiong X, Sun Y. DEPTOR, an mTOR inhibitor, is a physiological substrate of SCF (bTrCP) E3 ubiquitin ligase and regulates survival and autophagy. Molecular Cell. 2011; 44: 304-316.
51. Wei L, Gravitt PE, Song H, Maldonado AM, Ozbun MA. Nitric oxide induces early viral transcription coincident with increased DNA damage and mutation rates in Human Papillomavirus-infected cells. Cancer Research. 2009; 69:4878-84.
52. Manning BD. Balancing Akt with S6K: implications for both metabolic diseases and tumorigenesis. Journal of Cell Biology. 2004; 167: 399-403.
53. Um SH, Frigerio F, Watanabe M, Picard F, Joaquin M, Sticker M, Fumagalli S, Allegrini PR, Kozma SC, Auwerx J, Thomas G. Absence of S6K1 protects against age-and diet-induced obesity while enhancing insulin sensitivity. Nature. 2004; 431:200-205.
54. Manning BD, LogsdonMN, Lipovsky AI, Abbott D, Kwiatkowski DJ, Cantley LC. Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2. Genes and Development. 2005; 19: 1773-1778.
55. Gao D, Inuzuka H, Tan MK, Fukushima H, Locasale JW, Liu P, Wan L, Zhai B, Chin YR, Shaik S, Lyssiotis CA, Gygi SP, Toker A, Cantley LC, Asara JM, Harper JW, Wei W. mTOR drives its own activation via SCF(bTrCP)-dependent degradation of the mTOR inhibitor DEPTOR. Molecular Cell. 2011; 44: 290-303.
56. Carracedo A, Ma L, teruya-Feldstein J, Rojo F, Salmena L, Alimonti A, Egia A, Sasaki AT, Thomas G, Kozma SC, Papa A, Nardella C, Cantley LC, Baselga J, Pandolfi PP. Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer. Journal of Clinical Investigation. 2008; 118: 3065-3074.
57. Hadjal Y, Hadadeh O, Yazidi1 C, Barruet E, Binétruy B. A p38mapk-p53 cascade regulates mesodermal differentiation and neurogenesis of embryonic stem cells. Cell Death and Disease. 2013; 4:1-10.
58. Sima N, Cheng X, Ye F, Ma D, Xie X, Lu W. The overexpression of scaffolding protein NEDD9 promotesmigration and invasion in cervical cancer via tyrosine phosphorylated FAK and SRC. Plos one. 2013; 8: 1-12.
59. Khalifa YB, Teissier S, Marcus Tan MK, Phan QT, Daynac M, Wong WQ, Thierry F. The Human Papillomavirus E6 oncogene represses a cell adhesion pathway and disrupts focal adhesion through degradation of TAp63b upon transformation. Plos Pathogens. 2011; 7: 1-15.
60. Edinger AL, Linardic Cm, Chiang GG, Thompson CB, Abraham RT. Differential effects of rapamycin on mammalian target of rapamycin signaling functions in mammalian cells. Cancer Research. 2003; 63: 8451-8460.
61. Liu Q, Xu C, Kirubakaran S, Zhang X, Hur W, Liu Y, Kwiatkowski NP, Wang J, Westover KD, Gao P, Ercan D, Niepel M, Thoreen CC, Kang SA, Patricelli MP, Wang Y, Tupper T, Altabef A, Kawamura H, Held KD, Chou DM, Elledge Sj, Janne PA, Wong KK, Sabatini DM, Gray NS. Characterization of Torin2, an ATP-competitive inhibitor of mTOR, ATM, and ATR. Cancer Research. 2013; 73: 2574-2586.
62. Bakin AV, Safina A, Rinehart C, Daroqui C, Darbary H, Helfman DM. A Critical role of tropomyosins in TGF-regulation of the actin cytoskeleton and cell motility in epithelial cells. Molecular Biology of the Cell. 2004; 15: 4682-4694.
63. Yeh PY, Yeh KH, Chuang SE, Song YC, Cheng AL. Suppression of MEK/ERK signaling pathway enhances cisplatininduced NF-B activation by protein phosphatase 4-mediated NF-kB p65 Thr dephosphorylation. The Journal of Biological Chemistry. 2004; 279: 26143-26148.
64. Edmondson JM, Armstrong LS, Martinez AO. A rapid and simple MTT-based spectrophotometric assay for determining drug sensitivity in monolayer cultures. Journal of Tissue Culture Methods. 1998; 11: 15-17.
65. Goldstein JC, Munoz-Pinedo C, Ricci JE, Adams SR, Kelekar A, Schuler M, Tsien MY, Green DR. Cytochrome c is released in a single step during apoptosis. Cell Death and Differentiation. 2005; 12: 453-462.
66. Franken NA, Rodermond HM, Stap J, Haveman J, van Bree C. Clonogenic assay of cells in vitro. Nature Protocols. 2006; 1: 2315-2319.