| Project/Area Number |
26460272
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General anatomy (including histology/embryology)
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| Research Institution | Shinshu University |
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Principal Investigator |
FUJII Chifumi 信州大学, 学術研究院医学系, 助教 (10361982)
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| Co-Investigator(Renkei-kenkyūsha) |
TANIGUCHI Shun'ichiro 信州大学, 医学部, 特任教授 (60117166)
HIDA Shigeaki 名古屋市立大学, 大学院薬学研究科, 教授 (10345762)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 細胞運動 / 浸潤突起 / ASC / インフラマソーム / 細胞骨格 |
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| Outline of Final Research Achievements |
Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) has been reported a pro-apoptotic molecule that is epigenetically silenced in several human cancers. However, the role of ASC in the regulation of tumor progression remains elusive. To determine the effect of ASC depletion in cancer cells, ASC was stably knocked down in B16BL6, a murine melanoma cell line. ASC suppression increased the motility of B16BL6 cells and augmented invasiveness. Invadopodia formation and Src phosphorylation level were enhanced in ASC-knockdown cells as well. Since caspase-8 has been reported to enhance cellular migration by Tyr380 phosphorylation via Src, we examined Tyr380 phosphorylation of caspase-8 in ASC-knockdown cells and found it to be elevated. Moreover, ASC ablation increased pulmonary metastasis in mice after intravenous injection of B16BL6 cells. Our findings indicate that ASC suppresses cancer metastasis via the modulation of the Src-caspase-8 signaling pathway.
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