FAK alters invadopodia and focal adhesion composition and dynamics to regulate breast cancer invasion

Focal adhesion kinase (FAK) is important for breast cancer progression and invasion and is necessary for the dynamic turnover of focal adhesions. However, it has not been determined whether FAK also regulates the dynamics of invasive adhesions formed in cancer cells known as invadopodia. In this stu...

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Bibliographic Details
Published in:The Journal of cell biology 2009-04, Vol.185 (2), p.357-370
Main Authors: Chan, Keefe T, Cortesio, Christa L, Huttenlocher, Anna
Format: Article
Language:English
Subjects:
Antibodies
Biochemistry
Breast cancer
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cell adhesion & migration
Cell Line, Tumor
Cell lines
Cell motility
Cell Movement - physiology
Cell Surface Extensions - metabolism
Cells
Cultured cells
Female
Focal Adhesion Protein-Tyrosine Kinases - genetics
Focal Adhesion Protein-Tyrosine Kinases - metabolism
Focal adhesions
Focal Adhesions - metabolism
Gelatins
Humans
Kinases
Neoplasm Invasiveness
Oncology
Paxillin - genetics
Paxillin - metabolism
Phosphorylation
Physiological regulation
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
RNA, Small Interfering - genetics
RNA, Small Interfering - metabolism
Small interfering RNA
src-Family Kinases - metabolism
Tyrosine - metabolism
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Summary:Focal adhesion kinase (FAK) is important for breast cancer progression and invasion and is necessary for the dynamic turnover of focal adhesions. However, it has not been determined whether FAK also regulates the dynamics of invasive adhesions formed in cancer cells known as invadopodia. In this study, we report that endogenous FAK functions upstream of cellular Src (c-Src) as a negative regulator of invadopodia formation and dynamics in breast cancer cells. We show that depletion of FAK induces the formation of active invadopodia but impairs invasive cell migration. FAK-deficient MTLn3 breast cancer cells display enhanced assembly and dynamics of invadopodia that are rescued by expression of wild-type FAK but not by FAK that cannot be phosphorylated at tyrosine 397. Moreover, our findings demonstrate that FAK depletion switches phosphotyrosine-containing proteins from focal adhesions to invadopodia through the temporal and spatial regulation of c-Src activity. Collectively, our findings provide novel insight into the interplay between FAK and Src to promote invasion.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200809110