The adaptor protein Tks5/Fish is required for podosome formation and function, and for the protease-driven invasion of cancer cells.
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.
Seals
Darren F
DF
Van Andel Research Institute, Grand Rapids, Michigan 49503, USA.
Azucena
Eduardo F
EF
Pass
Ian
I
Tesfay
Lia
L
Gordon
Rebecca
R
Woodrow
Melissa
M
Resau
James H
JH
Courtneidge
Sara A
SA
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002645:Chickens; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D041681:NIH 3T3 Cells; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000378:metabolism; D018909:src Homology Domains; D019061:src-Family Kinases / Q000378:metabolism
D033942:Adaptor Proteins, Vesicular Transport; D034741:RNA, Small Interfering; C478582:SH3PXD2A protein, human; D019061:src-Family Kinases; D010447:Peptide Hydrolases