2005 Fiscal Year Final Research Report Summary
Signal transduction from α-catenin and the mechanism of growth suppression dependent on cell-cell adhesion.
| Project/Area Number |
16570162
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | Kagoshima University |
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Principal Investigator |
MATSUBARA Shyuichiro Kagoshima University, Frontier Science Research Center, Associate Professor, フロンテイアサイエンス研究推進センター, 助教授 (60199841)
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| Co-Investigator(Kenkyū-buntansha) |
OZAWA Masayuki Kagoshima University, Graduate School of Medical and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (90136854)
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| Project Period (FY) |
2004 – 2005
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| Keywords | α-catenin / cadherin / proliferation / compaction / cell-cell adhesion / signal transduction / multicellular spheroids / cell cycle regulators |
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| Research Abstract |
α-Catenin is an intracellular protein that associates with the carboxy-terminal region of cadherin, a cell adhesion molecule, via β-catenin or γ-catenin (plakoglobin). Linkage of cadherin to the cytoskeleton by catenins is required for full cadherin activity. Following transfection of an α-catenin-deficient colon carcinoma cell line with a series of α-catenin constructs, we discovered that the restoration of α-catenin expression results in reduced proliferation in three-dimensional multicellular spheroids, but not in two-dimensional monolayer cultures. The cellular function of α-catenin has not been compared between cells in three- and two-dimensional culture ; this is the first evidence that growth regulation in three-dimensional cultures requires signaling mediated by α-catenin. Two classes of constructs, containing deletions in either the central segment or the COOH terminus of the molecule, both induced morphological changes, including cell compaction, and suppressed cell growth in three-dimensional cultures. In α-catenin-expressing cells, inhibition of cadherin cell adhesion by treatment with anti-E-cadherin antibodies resulted in a similar phenotype as that observed following the loss of α-catenin. Therefore, both the homophilic interaction of the cadherin extracellular domain and the linkage of the cadherin cytoplasmic domain to the actin cytoskeleton by α-catenin are necessary for growth control in three-dimensional culture. Comparative analysis of cell cycle regulators revealed changes of expression and/or phosphorylation of these proteins.
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Research Products
(10 results)
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[Journal Article] Midkine promoter-driven suicide gene expression and -mediated adenovirus replication produced cytotoxic effects to immortalised and tumour cells.2004
Author(s)
Yu, L., Hamada, K., Namba, M., Kadomatsu, K., Muramatsu, T., Matsubara, S., Tagawa, M.
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Journal Title
Eur.J.Cancer 40-11
Pages: 1787-1794
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Midkine promoter can mediate transcriptional activation of a fused suicide gene in a broader range of human breast cancer compared with c-erbB-2 promoter.2004
Author(s)
Yu, L., Yamamoto, N., Kadomatsu, K., Muramatsu, T., Matsubara, S., Sakiyama, S., Tagawa M.
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Journal Title
Oncology 66-2
Pages: 143-149
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Insertion of an exogenous promoter in the E1A regulatory region of adenovirus does not disturb viral replication despite reduced E1A transcription.2004
Author(s)
Yu, L., Hamada, K., Namba, M., Kadomatsu, K., Muramatsu, T., Matsubara, S., Tagawa M.
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Journal Title
Cancer Lett. 203-1
Pages: 51-57
Description
「研究成果報告書概要(欧文)」より
