Structural basis for recognition of extracellular matrix remodeling by cancer cells
| Project/Area Number |
21770141
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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 |
Functional biochemistry
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 細胞・組織 / シグナル伝達 / 分子認識 / ミグナル伝達 |
|---|
| Research Abstract |
CD44 is a cell surface receptor for hyaluronan and is implicated in cancer invasion and metastasis. Proteolytic cleavage of CD44 plays a critical role in the migration of cancer cells and is regulated by factors present in the tumor microenvironment, such as hyaluronan oligosaccharides and epidermal growth factor. However, molecular mechanisms underlying the proteolytic cleavage on membranes remain poorly understood. In this study, we demonstrated that cholesterol depletion with methyl-・-cyclodextrin, which disintegrates membrane lipid rafts, enhances CD44 shedding mediated by a disintegrin and metalloproteinase 10(ADAM10), and that cholesterol depletion disorderes CD44 localization to the lipid raft. We also evaluated the effect of long-term cholesterol reduction using a statin agent, and demonstrated that statin enhances CD44 shedding and suppresses cancer cell migration on a hyaluronan-coated substrate. Our results indicate that membrane lipid organization regulates CD44 shedding, and propose a possible molecular mechanism by which cholesterol reduction might be effective for preventing and treating the cancer progression.
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Report
(4 results)
Research Products
(17 results)
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[Presentation] Direct ASEM immuno-electron microscopy of cells in solution2011
Author(s)
Tatsuhiko Ebihara, Toshiyuki Murai, Yuusuke Maruyama, Kazuhiro Mio, Sachie Manaka, Hidetoshi Nishiyama, Mitsuo Suga, and Chikara Sato
Organizer
World Congress on Advances in Oncology and International Symposium on Molecular Medicine
Place of Presentation
Hotel Rodos Palace(ギリシャ)
Year and Date
2011-10-06
Related Report
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