Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/69759
標題: Synergistic effect of focal adhesion kinase overexpression and hepatocyte growth factor stimulation on cell transformation
作者: Chan, P.C.
Liang, C.C.
Yu, K.C.
Chang, M.C.
Ho, W.L.
Chen, B.H.
Chen, H.C.
Project: Journal of Biological Chemistry
期刊/報告no:: Journal of Biological Chemistry, Volume 277, Issue 52, Page(s) 50373-50379.
摘要: 
Although an elevated level of focal adhesion kinase (FAK) has been observed in a variety of invasive human tumors, forced expression of FAK alone in cultured cells does not cause them to exhibit transformed phenotypes. Therefore, the role of FAK in oncogenic transformation remains unclear. In this study, we have demonstrated that FAK overexpression in Madin-Darby canine kidney epithelial cells rendered them susceptible to transformation by hepatocyte growth factor (HGF). Using various FAK mutants, we found that the simultaneous bindings of Src and p130(cas) were required for FAK to potentiate cell transformation. Expression of FAK-related nonkinase, kinase-deficient Src, or the Src homology 3 domain of p130(cas), which respectively serve as dominant negative versions of FAK, Src, and p130(cas), apparently reversed the transformed phenotypes of FAK-overexpressed cells upon HGF stimulation. Moreover, FAK overexpression was able to enhance HGF-elicited signals, leading to sustained activation of ERE, JNK, and AKT, which could be prevented by the expression of the Src homology 3 domain of p130(cas). Taken together, our results indicate that the synergistic effect of FAK overexpression and HGF stimulation leads to cell transformation and implicate a critical role of p130(cas) in this process.
URI: http://hdl.handle.net/11455/69759
ISSN: 0021-9258
DOI: 10.1074/jbc.M204691200
Appears in Collections:期刊論文

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