Activation of c-Src by receptor tyrosine kinases in human colon cancer cells with high metastatic potential

Weiguang Mao, Rosalyn Irby, Domenico Coppola, Ling Fu, Marek Wloch, Joel Turner, Hua Yu, Roy Garcia, Richard Jove, Timothy J. Yeatman

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175 Scopus citations

Abstract

Recent data suggest that signal transduction may have a critical role in the development and regulation of the metastatic phenotype. Here, we investigated the role of c-Src activation in the process of human colon cancer metastasis to the liver. Our data, derived from two different sets of human colon cancer cell line metastatic variants, suggest that not only do highly-metastatic cells display constitutively elevated c-Src protein kinase activity when compared to poorly metastatic cells, but also that receptor tyrosine kinases participate in the ligand-activation of c-Src above basal levels. Specifically, the epidermal growth factor receptor (EGFR), p185HER2/Neu and the hepatocyte growth factor receptor (c-Met) appear to be linked to the process because they preferentially activate c-Src in highly-metastatic cells. EGFR was found to associate with c-Src in colon cancer cells and specific inhibitors of the EGFR resulted in a reduction of c-Src activity to basal levels. In addition, c-Src transfectants displayed partially-activated EGFRs, suggesting a feedback role for c-Src in the regulation of the EGFR. p185HER2/Neu was also identified in immunocomplexes of c-Src following ligand activation of the EGFR, but only in highly-metastatic cells. Collectively, these observations suggest a paradigm whereby c-Src interacts with multiple cell-surface growth factors in a catalytic fashion for the development of tumor cells with metastatic potential.

Original languageEnglish (US)
Pages (from-to)3083-3090
Number of pages8
JournalOncogene
Volume15
Issue number25
DOIs
StatePublished - Dec 18 1997

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Mao, W., Irby, R., Coppola, D., Fu, L., Wloch, M., Turner, J., Yu, H., Garcia, R., Jove, R., & Yeatman, T. J. (1997). Activation of c-Src by receptor tyrosine kinases in human colon cancer cells with high metastatic potential. Oncogene, 15(25), 3083-3090. https://doi.org/10.1038/sj.onc.1201496