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Activated Src increases adhesion, survival and a2-integrin expression in human breast cancer cells

 Hee Boong PARK  ;  Vita GOLUBOVSKAYA  ;  William G. CANCE  ;  Rolf Joseph CRAVEN  ;  Sean SCULLY  ;  Jin Woo LEE  ;  Xihui YANG  ;  Lihui XU 
 BIOCHEMICAL JOURNAL, Vol.378(pt. 2) : 559-567, 2004 
Journal Title
Issue Date
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*
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.
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1. College of Medicine (의과대학) > Dept. of Orthopedic Surgery (정형외과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Jin Woo(이진우) ORCID logo https://orcid.org/0000-0002-0293-9017
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