Hedgehog signaling molecule SIL regulates the migration and progression of pancreatic ductal adenocarcinoma.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590456
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Aichi Medical University
• Principal Investigator: KASAI Kenji 愛知医科大学, 医学部, 准教授 (70242857)
• 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)
• Research Collaborator: ITO Hideaki 愛知医科大学, 医学部, 助教 (90711276)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: ヘッジホッグ / 膵臓癌 / SIL / 細胞運動 / ArhGEF7 / Pak1

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.

Free Research Field

人体病理