Activated Src increases adhesion, survival and α2-integrin expression in human breast cancer cells

Hee Boong Park, Vita Golubovskaya, Lihui Xu, Xihui Yang, Jin Woo Lee, Sean Scully, Rolf Joseph Craven, William G. Cance

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Focal adhesion kinase (FAK) is an intracellular kinase that localizes to focal adhesions. FAK is overexpressed in human tumours, and FAK regulates both cellular adhesion and anti-apoptotic survival signalling. Disruption of FAK function by overexpression of the FAK C-terminal domain [FAK-CD, analogous to the FRNK (FAK-related non-kinase) protein] leads to loss of adhesion and apoptosis in tumour cells. We have shown that overexpression of an activated form of the Src tyrosine kinase suppressed the loss of adhesion induced by dominant-negative; adenoviral FAK-CD and decreased the apoptotic response in BT474 and MCF-7 breast cancer cell lines. This adhesion-dependent apoptosis was increased by the Src-family kinase inhibitor PP2 {4-amino-5-(4-chlorophenyl)-7- (t-butyl)pyrazolo[3,4-d]pyrimidine}. We have also shown that expression of activated Src in breast cancer cells increased the expression of α2-integrin and that overexpression of α2-integrin suppressed FAK-CD-mediated loss of adhesion. Our results suggest a model in which Src regulates adhesion and survival through enhanced expression of the α2-integrin. This provides a mechanism through which Src promotes cellular adhesion and alters the adhesive function of FAK.

Original languageEnglish
Pages (from-to)559-567
Number of pages9
JournalBiochemical Journal
Volume378
Issue number2
DOIs
Publication statusPublished - 2004 Mar 1

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Park, H. B., Golubovskaya, V., Xu, L., Yang, X., Lee, J. W., Scully, S., Craven, R. J., & Cance, W. G. (2004). Activated Src increases adhesion, survival and α2-integrin expression in human breast cancer cells. Biochemical Journal, 378(2), 559-567. https://doi.org/10.1042/BJ20031392