Synergistic effect of focal adhesion kinase overexpression and hepatocyte growth factor stimulation on cell transformation

Po Chao Chan, Chun Chi Liang, Kuo Ching Yu, Ming Chen Chang, William L. Ho, Bor Huah Chen, Hong Chen Chen

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27 Citations (Scopus)


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 p130cas were required for FAK to potentiate cell transformation. Expression of FAK-related nonkinase, kinase-deficient Src, or the Src homology 3 domain of p130cas, which respectively serve as dominant negative versions of FAK, Src, and p130cas, 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 ERK, JNK, and AKT, which could be prevented by the expression of the Src homology 3 domain of p130cas. 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 p130cas in this process.

Original languageEnglish
Pages (from-to)50373-50379
Number of pages7
JournalJournal of Biological Chemistry
Issue number52
Publication statusPublished - 2002 Dec 27

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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