title: Activated Src increases adhesion, survival and alpha2-integrin expression in human breast cancer cells.
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 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.
authors: Department of Surgery, Ajou University School of Medicine, Seoul, South Korea.
authors: Hee Boong
authors: HB
authors: Park
authors: Vita
authors: V
authors: Golubovskaya
authors: Lihui
authors: L
authors: Xu
authors: Xihui
authors: X
authors: Yang
authors: Jin Woo
authors: JW
authors: Lee
authors: Sean
authors: S
authors: Scully
authors: Rolf Joseph
authors: RJ
authors: Craven
authors: William G
authors: WG
authors: Cance
mesh_terms: D017209:Apoptosis; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002470:Cell Survival; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D039421:Integrin alpha2 / Q000378:metabolism*; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; D039421:Integrin alpha2; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D016392:Proto-Oncogene Proteins pp60(c-src)