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.
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Research Article|
March 01 2004
Activated Src increases adhesion, survival and alpha2-integrin expression in human breast cancer cells
Hee Boong PARK;
Hee Boong PARK
1
*Department of Surgery, Ajou University School of Medicine, Seoul, South Korea
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Vita GOLUBOVSKAYA;
Vita GOLUBOVSKAYA
1
†Department of Surgery, University of Florida, Gainesville, FL 32610, U.S.A.
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Lihui XU;
Lihui XU
‡Lineberger Comprehensive Cancer Center and Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, U.S.A.
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Xihui YANG;
Xihui YANG
‡Lineberger Comprehensive Cancer Center and Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, U.S.A.
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Jin Woo LEE;
Jin Woo LEE
§Department of Orthopedic Surgery, Yonsei University College of Medicine, Seoul, South Korea
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Sean SCULLY, II;
Sean SCULLY, II
‖Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, U.S.A.
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Rolf Joseph CRAVEN;
Rolf Joseph CRAVEN
¶Department of Molecular and Biochemical Pharmacology, University of Kentucky, Lexington, KY, U.S.A.
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William G. CANCE
William G. CANCE
2
†Department of Surgery, University of Florida, Gainesville, FL 32610, U.S.A.
**Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, U.S.A.
2To whom correspondence should be addressed, at Department of Surgery, Health Science Center, P.O. Box 100286, 1600 SW Archer Road, Gainesville, FL 32610-0286, U.S.A. (e-mail cance@surgery.ufl.edu).
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Publisher: Portland Press Ltd
Received:
September 11 2003
Revision Received:
November 14 2003
Accepted:
November 20 2003
Accepted Manuscript online:
November 20 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2004
2004
Biochem J (2004) 378 (2): 559–567.
Article history
Received:
September 11 2003
Revision Received:
November 14 2003
Accepted:
November 20 2003
Accepted Manuscript online:
November 20 2003
Citation
Hee Boong PARK, Vita GOLUBOVSKAYA, Lihui XU, Xihui YANG, Jin Woo LEE, Sean SCULLY, Rolf Joseph CRAVEN, William G. CANCE; Activated Src increases adhesion, survival and alpha2-integrin expression in human breast cancer cells. Biochem J 1 March 2004; 378 (2): 559–567. doi: https://doi.org/10.1042/bj20031392
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