TY - JOUR
T1 - The adaptor protein Tks5/Fish is required for podosome formation and function, and for the protease-driven invasion of cancer cells
AU - Seals, Darren F.
AU - Azucena, Eduardo F.
AU - Pass, Ian
AU - Tesfay, Lia
AU - Gordon, Rebecca
AU - Woodrow, Melissa
AU - Resau, James H.
AU - Courtneidge, Sara A.
N1 - Funding Information:
We are grateful to Art Alberts for instruction in microinjection techniques and for coverslips, Bree Berghuis for cutting sections, Han-Mo Koo and Cindy Miranti for human cancer cell lines, Clare Abram for affinity-purified Tks5/Fish antibody, Marc Symons for advice on gelatin degradation assays, and Paul Bromann for review of the manuscript. This work was supported in part by institutional funds from the Van Andel Research Institute, and in part by a grant from the National Cancer Institute.
PY - 2005/2
Y1 - 2005/2
N2 - Tks5/Fish is a scaffolding protein with five SH3 domains and one PX domain. In Src-transformed cells, Tks5/Fish localizes to podosomes, discrete protrusions of the ventral membrane. We generated Src-transformed cells with reduced Tks5/Fish levels. They no longer formed podosomes, did not degrade gelatin, and were poorly invasive. We detected Tks5/Fish expression in podosomes in invasive cancer cells, as well as in human breast cancer and melanoma samples. Tks5/Fish expression was also required for protease-driven matrigel invasion in human cancer cells. Finally, coexpression of Tks5/Fish and Src in epithelial cells resulted in the appearance of podosomes. Thus, Tks5/Fish appears to be required for podosome formation, for degradation of the extracellular matrix, and for invasion of some cancer cells.
AB - Tks5/Fish is a scaffolding protein with five SH3 domains and one PX domain. In Src-transformed cells, Tks5/Fish localizes to podosomes, discrete protrusions of the ventral membrane. We generated Src-transformed cells with reduced Tks5/Fish levels. They no longer formed podosomes, did not degrade gelatin, and were poorly invasive. We detected Tks5/Fish expression in podosomes in invasive cancer cells, as well as in human breast cancer and melanoma samples. Tks5/Fish expression was also required for protease-driven matrigel invasion in human cancer cells. Finally, coexpression of Tks5/Fish and Src in epithelial cells resulted in the appearance of podosomes. Thus, Tks5/Fish appears to be required for podosome formation, for degradation of the extracellular matrix, and for invasion of some cancer cells.
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U2 - 10.1016/j.ccr.2005.01.006
DO - 10.1016/j.ccr.2005.01.006
M3 - Article
C2 - 15710328
AN - SCOPUS:13844264301
SN - 1535-6108
VL - 7
SP - 155
EP - 165
JO - Cancer Cell
JF - Cancer Cell
IS - 2
ER -