Inhibition of mTORC2 but not mTORC1 up-regulates E-cadherin expression and inhibits cell motility by blocking HIF-2α expression in human renal cell carcinoma

Journal of Urology

Volumn 189, Issue 5, 2013, Pages 1921-1929

  Maru, Shintaro ^b   Ishigaki, Yasuhito ^a   Shinohara, Nobuo ^b   Takata, Takanobu ^a   Tomosugi, Naohisa ^a   Nonomura, Katsuya ^b  

^a KANAZAWA MEDICAL UNIVERSITY   (Japan)

^b HOKKAIDO UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

Author keywords

cadherins; carcinoma, renal cell; endothelial PAS domain containing protein 1; mTORC2 complex, human; PP242

Indexed keywords

2 (4 AMINO 1 ISOPROPYL 1H PYRAZOLO[3,4 D]PYRIMIDIN 3 YL) 1H INDOL 5 OL; HYPOXIA INDUCIBLE FACTOR 2ALPHA; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; MESSENGER RNA; NERVE CELL ADHESION MOLECULE; PROTEIN ZO1; RAPAMYCIN; UVOMORULIN;

ARTICLE; CELL JUNCTION; CELL MIGRATION; CONTROLLED STUDY; HUMAN; HUMAN CELL; IMMUNOCYTOCHEMISTRY; IN VITRO STUDY; KIDNEY CARCINOMA; MICROSCOPY; PRIORITY JOURNAL; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; UPREGULATION; WESTERN BLOTTING; WOUND HEALING;

BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; CADHERINS; CARCINOMA, RENAL CELL; CELL MOVEMENT; HUMANS; KIDNEY NEOPLASMS; MULTIPROTEIN COMPLEXES; PROTEINS; TOR SERINE-THREONINE KINASES; TUMOR CELLS, CULTURED; UP-REGULATION;

EID: 84876293190     PISSN: 00225347     EISSN: 15273792     Source Type: Journal    
DOI: 10.1016/j.juro.2012.11.010     Document Type: Article

References (25)

1. J.R. Gnarra, K. Tory, Y. Weng Mutations of the VHL tumour suppressor gene in renal carcinoma Nat Genet 7 1994 85
2. K. Foster, A. Prowse, A. van den Berg Somatic mutations of the von Hippel-Lindau disease tumour suppressor gene in non-familial clear cell renal carcinoma Hum Mol Genet 3 1994 2169
3. W.G. Kaelin Jr The von Hippel-Lindau protein, HIF hydroxylation, and oxygen sensing Biochem Biophys Res Commun 338 2005 627
4. J.H. Ku, Y.H. Park, J.K. Myung Expression of hypoxia inducible factor-1alpha and 2alpha in conventional renal cell carcinoma with or without sarcomatoid differentiation Urol Oncol 29 2011 731
5. A. Toschi, E. Lee, N. Gadir Differential dependence of hypoxia-inducible factors 1 alpha and 2 alpha on mTORC1 and mTORC2 J Biol Chem 283 2008 34495
6. W.M. Linehan, R. Srinivasan, L.S. Schmidt The genetic basis of kidney cancer: a metabolic disease Nat Rev Urol 7 2010 277
7. G.L. Semenza Targeting HIF-1 for cancer therapy Nat Rev Cancer 3 2003 721
8. B. Krishnamachary, D. Zagzag, H. Nagasawa Hypoxia-inducible factor-1-dependent repression of E-cadherin in von Hippel-Lindau tumor suppressor-null renal cell carcinoma mediated by TCF3, ZFHX1A, and ZFHX1B Cancer Res 66 2006 2725
9. A.J. Evans, R.C. Russell, O. Roche VHL promotes E2 box-dependent E-cadherin transcription by HIF-mediated regulation of SIP1 and snail Mol Cell Biol 27 2007 157
10. M.A. Esteban, M.G. Tran, S.K. Harten Regulation of E-cadherin expression by VHL and hypoxia-inducible factor Cancer Res 66 2006 3567
11. A. Nagafuchi, S. Ishihara, S. Tsukita The roles of catenins in the cadherin-mediated cell adhesion: functional analysis of E-cadherin-alpha catenin fusion molecules J Cell Biol 127 1994 235
12. A. Cano, M.A. Perez-Moreno, I. Rodrigo The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression Nat Cell Biol 2 2000 76
13. W.J. Nelson, R. Nusse Convergence of Wnt, beta-catenin, and cadherin pathways Science 303 2004 1483
14. T. Shinojima, M. Oya, A. Takayanagi Renal cancer cells lacking hypoxia inducible factor (HIF)-1alpha expression maintain vascular endothelial growth factor expression through HIF-2alpha Carcinogenesis 28 2007 529
15. J.K. Maranchie, J.R. Vasselli, J. Riss The contribution of VHL substrate binding and HIF1-alpha to the phenotype of VHL loss in renal cell carcinoma Cancer Cell 1 2002 247
16. Y. Ishigaki, Y. Nakamura, T. Takehara Scanning electron microscopy with an ionic liquid reveals the loss of mitotic protrusions of cells during the epithelial-mesenchymal transition Microsc Res Tech 74 2011 1024
17. C.A. Sparks, D.A. Guertin Targeting mTOR: prospects for mTOR complex 2 inhibitors in cancer therapy Oncogene 29 2010 3733
18. K.E. O'Reilly, F. Rojo, Q.B. She mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt Cancer Res 66 2006 1500
19. D.D. Sarbassov, D.A. Guertin, S.M. Ali Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex Science 307 2005 1098
20. D.C. Cho, M.B. Cohen, D.J. Panka The efficacy of the novel dual PI3-kinase/mTOR inhibitor NVP-BEZ235 compared with rapamycin in renal cell carcinoma Clin Cancer Res 16 2010 3628
21. S. Liu, S.M. Kumar, H. Lu MicroRNA-9 up-regulates E-cadherin through inhibition of NF-kappaB1-Snail1 pathway in melanoma J Pathol 226 2012 61
22. A. Katagiri, R. Watanabe, Y. Tomita E-cadherin expression in renal cell cancer and its significance in metastasis and survival Br J Cancer 71 1995 376
23. E. Batlle, E. Sancho, C. Francí The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells Nat Cell Biol 2 2000 84
24. M.J. Wheelock, Y. Shintani, M. Maeda Cadherin switching J Cell Sci 121 2008 727
25. R.B. Hazan, G.R. Phillips, R.F. Qiao Exogenous expression of N-cadherin in breast cancer cells induces cell migration, invasion, and metastasis J Cell Biol 148 2000 779