The COOH-terminal domain of the focal adhesion kinase induces loss of adhesion and cell death in human tumor cells.
Focal adhesion kinase (FAK) is a tyrosine kinase that is linked to signaling pathways between cells and their extracellular matrix. An alternate transcript of the COOH-terminal region of the FAK gene, called FAK-related nonkinase, has been shown to act as an inhibitor of FAK in chicken embryo fibroblasts. We have designed an analogous segment of human FAK, FAK COOH-terminal domain (FAK-CD), and transfected this construct into human tumor cells. Expression of FAK-CD inhibited cell growth in BT474 human breast cancer cells and C8161 human melanoma cells. To characterize the nature of growth inhibition, we developed an inducible system of FAK-CD expression and demonstrated that the induced FAK-CD protein localized to focal adhesions, causing cellular rounding, an irreversible loss of adhesion, and subsequent cell death. In addition, expression of FAK-CD reduced tyrosine phosphorylation of FAK, suggesting that FAK-CD may be a potent inhibitor of FAK in human tumor cells.
Xu
L H
LH
Department of Surgery, University of North Carolina at Chapel Hill School of Medicine, 27599, USA.
Yang
X
X
Craven
R J
RJ
Cance
W G
WG
D017398:Alternative Splicing / Q000235:genetics; D017209:Apoptosis / Q000235:genetics*; D002448:Cell Adhesion / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000032:analysis; D004790:Enzyme Induction / Q000235:genetics; D005455:Fluorescent Antibody Technique; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D051419:Paxillin; D010750:Phosphoproteins / Q000032:analysis; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D014162:Transfection / Q000235:genetics; D014407:Tumor Cells, Cultured; D015032:Zinc / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; 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; D015032:Zinc