2012 Fiscal Year Final Research Report
Claudin 1 mediates TNFα-induced gene expression and cell migration in human gastric cancer cells.
| Project/Area Number |
22591464
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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 |
Digestive surgery
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
NAITO Kazuyo 京都府立医科大学, 医学研究科, 教授 (90164102)
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| Co-Investigator(Kenkyū-buntansha) |
OTSUJI Eigo 京都府立医科大学, 医学研究科, 教授 (20244600)
SHIOZAKI Atsushi 京都府立医科大学, 医学研究科, 助教 (40568086)
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| Project Period (FY) |
2010 – 2012
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| Keywords | 胃癌 / TNF-α / Claudin-1 |
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| Research Abstract |
TNFα has been known to be produced in cancer cells as an endogenous tumor promoter, and involved in epithelial-mesenchymal transition. However, Claudin-1 is well known as one of tight junction proteins, recent studies also showed that the expression of Claudin-1 increased during tumor progression in cancer cells. In this study, we investigated the association between TNFα and Claudin-1 during tumor progression in human gastric cancer cells. Claudin-1 was significantly increased upon TNFα treatment in gastric cancer cells, and down-regulation of Claudin-1 using siRNA inhibited 70% of TNFα-induced gene expression and 87% of microRNA expression. Further, knocking-down of Claudin-1 decreased cell proliferation, migration and invasion, and increased apoptosis. Pathway analysis showed that cellular movement, including MMP7, TGFBR1 and TNFSF10, was the top-ranked signal network. In conclusion, Claudin-1 behaves as a crucial signal mediator in TNFα-induced gene expression and cell migration in gastric cancer cells.
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