Abstract | AIMS: METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that Pyk2 transformed the epithelial HCC cell line Hep3B into a mesenchymal phenotype via the induction of epithelial to mesenchymal transition (EMT), signified by the up-regulation of membrane ruffle formation, activation of Rac/ Rho GTPases, down-regulation of epithelial genes E-cadherin and cytokeratin as well as promotion of cell motility in presence of lysophosphatidic acid (LPA). Suppression of Pyk2 by overexpression of dominant negative PRNK domain in the metastatic HCC cell line MHCC97L transformed its fibroblastoid phenotype to an epithelial phenotype with up-regulation of epithelial genes, down-regulation of mesenchymal genes N-cadherin and STAT5b, and reduction of LPA-induced membrane ruffle formation and cell motility. Moreover, overexpression of Pyk2 in Hep3B cells promoted the phosphorylation and localization of mesenchymal gene Hic-5 onto cell membrane while suppression of Pyk2 in MHCC97L cells attenuated its phosphorylation and localization. CONCLUSION: These data provided new evidence of the underlying mechanism of Pyk2 in controlling cell motility of HCC cells through regulation of genes associated with EMT.
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Authors | Chris K Sun, Kevin T Ng, Zophia X Lim, Qiao Cheng, Chung Mau Lo, Ronnie T Poon, Kwan Man, Nathalie Wong, Sheung Tat Fan |
Journal | PloS one
(PLoS One)
Vol. 6
Issue 4
Pg. e18878
(Apr 20 2011)
ISSN: 1932-6203 [Electronic] United States |
PMID | 21533080
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cadherins
- STAT5 Transcription Factor
- Keratins
- Focal Adhesion Kinase 2
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Topics |
- Cadherins
(metabolism)
- Carcinoma, Hepatocellular
(enzymology, pathology, ultrastructure)
- Cell Line, Tumor
- Cell Movement
(physiology)
- Down-Regulation
- Epithelial-Mesenchymal Transition
(physiology)
- Focal Adhesion Kinase 2
(metabolism, physiology)
- Focal Adhesions
- Humans
- Keratins
(metabolism)
- Liver Neoplasms
(enzymology, pathology, ultrastructure)
- Microscopy, Electron, Scanning
- STAT5 Transcription Factor
(metabolism)
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