2009 Fiscal Year Final Research Report
The lipid raft-anchored adaptor protein Cbp controls the oncogenic potential of c-Src
| Project/Area Number |
20790253
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
ONEYAMA Chitose Osaka University, 微生物病研究所, 助教 (90373208)
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| Project Period (FY) |
2008 – 2009
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| Keywords | Src / Csk / Cbp / トランスフォーメーション |
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| Research Abstract |
The tyrosine kinase c-Src is upregulated in various human cancers irrespective of its negative regulator Csk, but the regulatory mechanisms remain unclear. In this study, we show that a lipid raft-anchored Csk adaptor, Cbp/PAG, is directly involved in controlling the oncogenicity of c-Src. Using Csk-deficient cells that can be transformed by c-Src overexpression, we found that Cbp expression is markedly downregulated by c-Src activation and re-expression of Cbp efficiently suppresses c-Src transformation as well as tumorigenesis. Cbp-deficient cells are more susceptible to v-Src transformation than their parental cells. Upon phosphorylation, Cbp specifically binds to activated c-Src and sequesters it in lipid rafts, resulting in an efficient suppression of c-Src function independent of Csk. In some human cancer cells and tumors, Cbp is downregulated and the introduction of Cbp significantly suppresses tumorigenesis. These findings indicate a potential role for Cbp as a suppressor of c-Src-mediated tumor progression.
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Research Products
(9 results)
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[Journal Article] Autonomous regulation of osteosarcoma cell invasiveness by Wnt5a/Ror2 signaling2009
Author(s)
Enomoto M, Hayakawa S, Itsukushima S, Ren DY, Matsuo M, Tamada K, Oneyama C, Okada M, Takumi T, Nishita M, Minami Y
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Journal Title
Oncogene 28(36)
Pages: 3197-3208
Peer Reviewed
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