4.7 Article

WTAP regulates migration and invasion of cholangiocarcinoma cells

Journal

JOURNAL OF GASTROENTEROLOGY
Volume 48, Issue 11, Pages 1271-1282

Publisher

SPRINGER JAPAN KK
DOI: 10.1007/s00535-013-0748-7

Keywords

WTAP; Migration; Invasion; Cholangiocarcinoma

Funding

  1. Medical Research Institute [2009-22]
  2. Pusan National University Hospital
  3. medical research centre program of Ministry of Education, Science and Technology/Korea Science and Engineering Foundation [2011-0006190]
  4. National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea [0920050]

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Wilms' tumor 1-associating protein (WTAP) is a nuclear protein that has been associated with the regulation of proliferation and apoptosis. Although its dynamic expression and physiological functions in vascular cells have been reported, its expression and roles in cholangiocarcinoma cells are poorly characterized. To examine the expression of WTAP in patient tissues, we performed immunohistochemistry. To examine motility of cholangiocarcinoma cells, we employed Boyden chamber, wound healing and Matrigel invasion assays, and a liver xenograft model. Immunohistochemistry in patient tissues showed WTAP overexpression in cholangiocarcinoma tissues and correlation of WTAP expression with metastasis of cholangiocarcinoma cells. Overexpression or knockdown of WTAP significantly increased or decreased the motility of cholangiocarcinoma cells. Moreover, WTAP overexpression or knockdown significantly increased or decreased tumorigenicity of cholangiocarcinoma cells in an orthotopic xenograft model. Furthermore, microarray study showed that WTAP induce the expressions of MMP7, MMP28, cathepsin H and Muc1. WTAP is overexpressed in cholangiocarcinoma and regulates motility of cholangiocarcinoma cells.

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