2013 Fiscal Year Final Research Report
Regulation of tumor growth via intracellular membrane compartments
| Project/Area Number |
22240088
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Osaka University |
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Principal Investigator |
OKADA Masato 大阪大学, 微生物病研究所, 教授 (10177058)
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| Project Period (FY) |
2010-04-01 – 2014-03-31
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| Keywords | 腫瘍増殖 / シグナル伝達 / リソソーム / ラフト / mTOR / 足場タンパク質 |
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| Research Abstract |
Tumor growth is promoted by persistent activation of growth signaling, which is caused by mutations of various proto-oncogenes. In this study, we investigated the function and regulation mechanisms of the major growth signaling pathways, the MAPK and mTOR pathways, via the scaffold protein p18 that is anchored to the surface of lysosomes. Using p18 knockout cells and mice, we found that p18 forms a regulatory complex (Ragulator) required for activation of mTORC1, and plays crucial roles in regulating cell growth, proliferation, differentiation, and tumor growth. We also clarified the roles of the p18-mTORC1 pathway in the regulation of cell cycle via the transcription factor FoxO3a and lysosome-mediated catabolism. These finding shed new lights on the roles of the intracellular membrane compartments, e.g. lysosomes, in the regulation of tumor promoting signaling.
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[Journal Article] MiR-424/503-mediated Rictor upregulation promotes tumor progression2013
Author(s)
Oneyama C, Kito Y, Asai R, Ikeda J, Yoshida T, Okuzaki D, Kokuda R, Kakumoto K, Takayama K, Inoue S, Morii E, Okada M.
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Journal Title
PLos ONE 2013
Volume: 8(11)
Pages: e80300
DOI
Peer Reviewed
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[Journal Article] Identification of a new interaction mode between the Src homology 2 domain of C-terminal Src kinase (Csk) and Csk-binding protein/phosphoprotein associated with glycosphingolipid microdomains2013
Author(s)
Tanaka H, Akagi K, Oneyama C, Tanaka M, Sasaki Y, Kanou T, Lee YH, Yokogawa D, Dobenecker MW, Nakagawa A, Okada M, Ikegami T
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Journal Title
J Biol Chem 2013
Volume: 288(21)
Pages: 15240-54
DOI
Peer Reviewed
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[Journal Article] MicroRNA-mediated upregulation of integrin-linked kinase promotes Src-induced tumor progression2012
Author(s)
Oneyama C, Morii E, Okuzaki D, Takahashi Y, Ikeda J, Wakabayashi N, Akamatsu H, Tsujimoto M, Nishida T, Aozasa K, Okada M
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Journal Title
Oncogene 2012
Volume: 31(13)
Pages: 1623-35
DOI
Peer Reviewed
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