2013 Fiscal Year Final Research Report
Control of tumor progression by targeting the lipid rafts
| Project/Area Number |
24659150
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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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 |
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | ラフト / Src |
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| Research Abstract |
In c-Src-induced transformation, we found that c-Src up-regulation perturbs sphingolipid/cholesterol-enriched membrane microdomains (lipid rafts) by activating ceramide synthesis and downregulation of cholesterol, resulting in promotion of c-Src translocation to focal adhesions. Inhibition of ceramide conversion into glucosylceramide promotes liberation of c-Src from microdomains, and inhibition of de novo ceramide synthesis restores the microdomain distribution of c-Src and suppresses c-Src-induced transformation. We tested whether alteration of the cholesterol content of lipid rafts in c-Src-dependent cell membranes affects tumor progression in vivo. We found simvastatin, a cholesterol synthesis inhibitor, lowered raft cholesterol content, promoted tumorigenicity of colon cancer cells. These results suggest that ceramide and cholesterol could be critical modifiers of tumor progression probably by modulating lipid rafts function.
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[Journal Article] Identification of a new interaction mode between the Src homology 2 (SH2) domain of C-terminal Src kinase (Csk) and Csk-binding protein (Cbp)/phosphoprotein associated with glycosphingolipid microdomains (PAG)2013
Author(s)
T anaka H, Akagi KI, 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
Volume: 288(21)
Pages: 15240-54
DOI
Peer Reviewed
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[Journal Article] MicroRNA-mediated upregulation of integrin-linked kinase is crucial for 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
Volume: 31
Pages: 1623-1635
DOI
Peer Reviewed
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[Presentation] Hisataka Sabe「Mechanisms by which p53 alterations generate GEP100-Arf6-AMAP1 pathway as a mesenchymal invasion machinery to be activated by RTK-ligands and TGF-beta1」2013
Author(s)
Ari Hashimoto, Shigeru Hashimoto, Yasuhito Onodera, Tsukasa Oikawa, Chitose Oneyama, RumikoKinoshita, Jin-Min Nam, Mishie Tanino, Hirokzu Sugino, Ayumu Yoshikawa, Yutaro Otsuka, Haruka Handa, Masanao Yoshino, Hiroki Sato, Satoshi Fukuda, Shinya Tanaka, Hiroki Shirato, Yoichi Ito, Masato Okada
Organizer
第36回日本分子生物学会年会
Year and Date
2013-12-04
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