Focal adhesion kinase is not required for Src-induced formation of invadopodia in KM12C colon cancer cells and can interfere with their assembly.
Overexpression of active Src induces invadopodia formation and associated matrix degradation in KM12C colon cancer cells. FAK is present with active Src at sites of matrix-degrading activity (invadopodia), specifically residing in rings surrounding the cortactin-containing invadopodia cores. Since FAK is a key effector protein in many aspects of Src function, we addressed whether FAK is necessary for Src-induced invadopodia formation and matrix degradation in KM12C colon cancer cells. We found that efficient knockdown of FAK expression by siRNA had no effect on invadopodia formation or matrix degradation. However, overexpression of FAK could actually suppress invadopodia formation and matrix degradation. FAK phosphorylation on the putative auto-phosphorylation tyrosine 397 and the Src-specific sites are all required for overexpressed FAK to inhibit invadopodia formation, while the kinase activity of exogenous FAK is apparently not required. These data imply that kinase activities other than FAK auto-phosphorylation may contribute to the phosphorylation of FAK tyrosine 397 in some contexts to promote an activity of FAK that can counteract invadopodia formation. Further work is required to determine how the strength of signalling through FAK suppresses invadopodia, but we propose that FAK controls the balance of adhesion types in cells, and that this is one of the determinants of whether a cancer cell can make stable matrix-degrading invadopodia.
Vitale
Sebastien
S
The Beatson Institute for Cancer Research, Garscube Estate, Bearsden, Glasgow, UK.
Avizienyte
Egle
E
Brunton
Valerie G
VG
Frame
Margaret C
MC
D008841:Actin Cytoskeleton / Q000201:enzymology* / Q000648:ultrastructure; D002448:Cell Adhesion; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology*; D005109:Extracellular Matrix / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D015398:Signal Transduction; D018909:src Homology Domains
D051416:Focal Adhesion Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src)