WTAP regulates migration and invasion of cholangiocarcinoma cells.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
WTAP is overexpressed in cholangiocarcinoma and regulates motility of cholangiocarcinoma cells.
Departments of Surgery, School of Medicine, Pusan National University, Busan, Republic of Korea.
Hong-Jae
HJ
Jo
Hye-Eun
HE
Shim
Myoung-Eun
ME
Han
Hyun-Jung
HJ
Kim
Ki-Sun
KS
Kim
Sungmin
S
Baek
Kyung-Un
KU
Choi
Gi-Yeong
GY
Hur
Sae-Ock
SO
Oh
D000818:Animals; D001650:Bile Duct Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic; D018797:Cell Cycle Proteins; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D003094:Collagen; D015194:Diffusion Chambers, Culture; D004338:Drug Combinations; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D007797:Laminin; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000502:physiology*; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000502:physiology*; D011509:Proteoglycans; D000072260:RNA Splicing Factors; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics
D018797:Cell Cycle Proteins; D004338:Drug Combinations; D007797:Laminin; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011509:Proteoglycans; D000072260:RNA Splicing Factors; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C419554:WTAP protein, human; C059485:matrigel; D003094:Collagen