Activated Src increases adhesion, survival and alpha2-integrin expression in human breast cancer cells

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, analogo...

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Bibliographic Details
Published in:Biochemical journal 2004-03, Vol.378 (Pt 2), p.559-567
Main Authors: Park, Hee Boong, Golubovskaya, Vita, Xu, Lihui, Yang, Xihui, Lee, Jin Woo, Scully, 2nd, Sean, Craven, Rolf Joseph, Cance, William G
Format: Article
Language:English
Subjects:
Apoptosis
Breast Neoplasms - enzymology
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cell Adhesion
Cell Line, Tumor
Cell Survival
Cytoskeletal Proteins - metabolism
Enzyme Activation
Female
Focal Adhesion Kinase 1
Focal Adhesion Protein-Tyrosine Kinases
Humans
Integrin alpha2 - metabolism
Paxillin
Phosphoproteins - metabolism
Protein Structure, Tertiary
Protein-Tyrosine Kinases - chemistry
Protein-Tyrosine Kinases - metabolism
Proto-Oncogene Proteins pp60(c-src) - metabolism
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Summary: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 alpha2-integrin and that overexpression of alpha2-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 alpha2-integrin. This provides a mechanism through which Src promotes cellular adhesion and alters the adhesive function of FAK.
ISSN:0264-6021
1470-8728
DOI:10.1042/BJ20031392