Targeting mTORC2 inhibits colon cancer cell proliferation in vitro and tumor formation in vivo

Molecular Cancer

Volumn 9, Issue , 2010, Pages

  Roulin, Didier ^a   Cerantola, Yannick ^a   Dormond Meuwly, Anne ^a   Demartines, Nicolas ^a   Dormond, Olivier ^a  

^a LAUSANNE UNIVERSITY HOSPITAL   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; RNA; CARRIER PROTEIN; CRTC2 PROTEIN, HUMAN; PROTEIN; RAPTOR PROTEIN, HUMAN; RICTOR PROTEIN, HUMAN; TRANSCRIPTION FACTOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CARCINOGENESIS; CELL CYCLE ARREST; CELL CYCLE G1 PHASE; CELL PROLIFERATION; CELL STRAIN HT29; COLON CANCER; CONTROLLED STUDY; DOWN REGULATION; GENE EXPRESSION; GENE SILENCING; GENE TARGETING; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; ANIMAL; COLON TUMOR; DRUG SCREENING; HUMAN; METABOLISM; PATHOLOGY; TUMOR CELL LINE;

MAMMALIA; MUS MUSCULUS;

ANIMALS; CARRIER PROTEINS; CELL LINE, TUMOR; CELL PROLIFERATION; COLONIC NEOPLASMS; DOWN-REGULATION; GENE KNOCKDOWN TECHNIQUES; HUMANS; MICE; PROTEINS; TRANSCRIPTION FACTORS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 77952305228     PISSN: None     EISSN: 14764598     Source Type: Journal    
DOI: 10.1186/1476-4598-9-57     Document Type: Article

References (15)

1. Wullschleger S, Loewith R, Hall MN. TOR signaling in growth and metabolism. Cell 2006, 124:471-484. 10.1016/j.cell.2006.01.016, 16469695.
2. Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev 2004, 18:1926-1945. 10.1101/gad.1212704, 15314020.
3. Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell 2007, 12:9-22. 10.1016/j.ccr.2007.05.008, 17613433.
4. Sarbassov DD, Ali SM, Sengupta S, Sheen JH, Hsu PP, Bagley AF, Markhard AL, Sabatini DM. Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 2006, 22:159-168. 10.1016/j.molcel.2006.03.029, 16603397.
5. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 2005, 307:1098-1101. 10.1126/science.1106148, 15718470.
6. Jacinto E, Loewith R, Schmidt A, Lin S, Ruegg MA, Hall A, Hall MN. Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol 2004, 6:1122-1128. 10.1038/ncb1183, 15467718.
7. Faivre S, Kroemer G, Raymond E. Current development of mTOR inhibitors as anticancer agents. Nat Rev Drug Discov 2006, 5:671-688. 10.1038/nrd2062, 16883305.
8. Masri J, Bernath A, Martin J, Jo OD, Vartanian R, Funk A, Gera J. mTORC2 activity is elevated in gliomas and promotes growth and cell motility via overexpression of rictor. Cancer Res 2007, 67:11712-11720. 10.1158/0008-5472.CAN-07-2223, 18089801.
9. Guertin DA, Stevens DM, Saitoh M, Kinkel S, Crosby K, Sheen JH, Mullholland DJ, Magnuson MA, Wu H, Sabatini DM. mTOR complex 2 is required for the development of prostate cancer induced by Pten loss in mice. Cancer Cell 2009, 15:148-159. 10.1016/j.ccr.2008.12.017, 2701381, 19185849.
10. Rychahou PG, Kang J, Gulhati P, Doan HQ, Chen LA, Xiao SY, Chung DH, Evers BM. Akt2 overexpression plays a critical role in the establishment of colorectal cancer metastasis. Proc Natl Acad Sci USA 2008, 105:20315-20320. 10.1073/pnas.0810715105, 2629319, 19075230.
11. Zhang YJ, Dai Q, Sun DF, Xiong H, Tian XQ, Gao FH, Xu MH, Chen GQ, Han ZG, Fang JY. mTOR signaling pathway is a target for the treatment of colorectal cancer. Ann Surg Oncol 2009, 16:2617-2628. 10.1245/s10434-009-0555-9, 19517193.
12. Fujishita T, Aoki K, Lane HA, Aoki M, Taketo MM. Inhibition of the mTORC1 pathway suppresses intestinal polyp formation and reduces mortality in ApcDelta716 mice. Proc Natl Acad Sci USA 2008, 105:13544-13549. 10.1073/pnas.0800041105, 2533226, 18768809.
13. Thoreen CC, Kang SA, Chang JW, Liu Q, Zhang J, Gao Y, Reichling LJ, Sim T, Sabatini DM, Gray NS. An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J Biol Chem 2009, 284:8023-8032. 10.1074/jbc.M900301200, 2658096, 19150980.
14. Feldman ME, Apsel B, Uotila A, Loewith R, Knight ZA, Ruggero D, Shokat KM. Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. PLoS Biol 2009, 7:e38. 10.1371/journal.pbio.1000038, 2637922,2637922, 19209957.
15. Yu K, Toral-Barza L, Shi C, Zhang WG, Lucas J, Shor B, Kim J, Verheijen J, Curran K, Malwitz DJ, et al. Biochemical, cellular, and in vivo activity of novel ATP-competitive and selective inhibitors of the mammalian target of rapamycin. Cancer Res 2009, 69:6232-6240. 10.1158/0008-5472.CAN-09-0299, 19584280.