The adaptor protein Tks5/Fish is required for podosome formation and function, and for the protease-driven invasion of cancer cells

Darren F. Seals, Eduardo F. Azucena, Ian Pass, Lia Tesfay, Rebecca Gordon, Melissa Woodrow, James H. Resau, Sara A. Courtneidge

Research output: Contribution to journalArticle

246 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)155-165
Number of pages11
JournalCancer Cell
Volume7
Issue number2
DOIs
StatePublished - Feb 2005

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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