Regulation of cell motility by poly(ADP-ribosyl)ation and its application to overcoming cancer invasion and metastasis
| Project/Area Number |
26640109
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor therapeutics
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| Research Institution | Japanese Foundation for Cancer Research |
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Principal Investigator |
Seimiya Hiroyuki 公益財団法人がん研究会, がん化学療法センター分子生物治療研究部, 部長 (50280623)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | ポリ(ADP-リボシル)化 / 細胞運動 / アクチン / がん / 浸潤 / 細胞分裂 / 転移 |
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| Outline of Final Research Achievements |
This study aims to elucidate the functional involvement of TAB182, a binding partner of tankyrase poly(ADP-ribose) polymerase, in cell motility and invasion and its molecular mechanism. We found that TAB182 negatively regulates cancer cell motility and invasion. We identified X, a regulator of actin dynamics, as a novel TAB182-binding protein. Depletion of either TAB182 or X induced phosphorylation of cofilin, a destabilizer of the actin filaments, and enhanced cell motility and invasion. These phenomena were also induced by tankyrase overexpression and inhibited by a tankyrase inhibitor. In clinical settings, TAB182 expression was reduced in the invasive areas of pancreatic cancer. These observations suggest that aberrant expression of TAB182 may facilitate cancer cell invasion.
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Report
(3 results)
Research Products
(11 results)
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[Journal Article] Comprehensive transcriptomic analysis of molecularly targeted drugs in cancer for target pathway evaluation2015
Author(s)
Mashima T, Ushijima M, Matsuura M, Tsukahara S, Kunimasa K, Furuno A, Saito S, Kitamura M, Soma-Nagae T, Seimiya H, Dan S, Yamori T, Tomida A
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Journal Title
Cancer Science
Volume: in press
Issue: 7
Pages: 909-920
DOI
Related Report
Peer Reviewed / Open Access
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