| Project/Area Number |
24590456
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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 |
Human pathology
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| Research Institution | Aichi Medical University |
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Principal Investigator |
KASAI Kenji 愛知医科大学, 医学部, 准教授 (70242857)
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| Co-Investigator(Renkei-kenkyūsha) |
INAGUMA Shingo 愛知医科大学, 医学部, 講師 (80410786)
IKEDA Hiroshi 愛知医科大学, 医学部, 教授 (00131219)
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| Research Collaborator |
ITO Hideaki 愛知医科大学, 医学部, 助教 (90711276)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | ヘッジホッグ / 膵臓癌 / SIL / 細胞運動 / ArhGEF7 / Pak1 / 分子病理 |
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| Outline of Final Research Achievements |
Cell migration depends on a sequential modification of cytoskeletal complex, which is triggered by the accumulation and activation of ArhGEF7-Pak complex to lamellipodia/filopodia of the cells. In this sutdy, we revealed that SIL/STIL, a cytoplasmic molecule involved in the Hedgehog signaling and over-expressed in human pancreatic cancers, associated with ArhGEF7-Pak1 complex. SIL localized in lamellipodia of huamn pancreatic cancer cell lines along with RAC1,ArhGEF7 and Pak1. SIL-Knockdowned cells harbored enlarged cytoplasm lacking RAC1 and ArhGEF7-Pak1 accumulation in the cell front, which mimiced ArhGEF7-knockdown, and reduced the motility. Furthermore, SIL knockdown-induced reduction of the motility was not rescued by Tet-regulated induction of Pak1 T423E mutant in human pancreatic cancer cell line PANC-1. These evidences indicated an indispensable role of SIL in regulating the subcellular localization of ArhGEF7-Pak1 complex and the cellular movement of pancreatic cancer cells.
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