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

Cancer Cell. 2005 Feb;7(2):155-65. doi: 10.1016/j.ccr.2005.01.006.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Vesicular Transport / metabolism
  • Adaptor Proteins, Vesicular Transport / physiology*
  • Animals
  • Breast Neoplasms / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Chickens
  • Extracellular Matrix / metabolism
  • Humans
  • Melanoma / metabolism
  • Mice
  • Microscopy, Fluorescence
  • NIH 3T3 Cells
  • Neoplasm Invasiveness
  • Neoplasms / metabolism*
  • Peptide Hydrolases / chemistry*
  • Protein Structure, Tertiary
  • RNA, Small Interfering / metabolism
  • src Homology Domains
  • src-Family Kinases / metabolism


  • Adaptor Proteins, Vesicular Transport
  • RNA, Small Interfering
  • SH3PXD2A protein, human
  • src-Family Kinases
  • Peptide Hydrolases