RACK1 inhibits the serum- and anchorage-independent growth of v-Src transformed cells

FEBS Lett. 2004 Jun 4;567(2-3):321-6. doi: 10.1016/j.febslet.2004.03.125.

Abstract

Cancer cells are capable of serum- and anchorage-independent growth, and focus formation on monolayers of normal cells. Previously, we showed that RACK1 inhibits c-Src kinase activity and NIH3T3 cell growth. Here, we show that RACK1 partially inhibits v-Src kinase activity, and the serum- and anchorage-independent growth of v-Src transformed cells, but has no effect on focus formation. RACK1-overexpressing v-Src cells show disassembly of podosomes, which are actin-rich structures that are distinctive to fully transformed cells. Together, our results demonstrate that RACK1 overexpression in v-Src cells partially reverses the transformed phenotype of the cells. Our results identify an endogenous inhibitor of the oncogenic Src tyrosine kinase and of cell transformation.

Publication types

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

MeSH terms

  • Actins / metabolism
  • Actins / ultrastructure
  • Animals
  • Cell Adhesion / physiology
  • Cell Count
  • Cell Division / physiology
  • Cell Line, Transformed
  • Culture Media
  • Cytoskeletal Proteins / metabolism
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Mice
  • NIH 3T3 Cells
  • Oncogene Protein pp60(v-src) / antagonists & inhibitors
  • Oncogene Protein pp60(v-src) / genetics
  • Oncogene Protein pp60(v-src) / metabolism*
  • Paxillin
  • Peptides / genetics
  • Peptides / metabolism
  • Peptides / physiology*
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Kinase C / physiology
  • Protein-Tyrosine Kinases / metabolism
  • Receptors for Activated C Kinase
  • Serum
  • Transfection
  • Transformation, Genetic
  • Tyrosine / metabolism

Substances

  • Actins
  • Culture Media
  • Cytoskeletal Proteins
  • Paxillin
  • Peptides
  • Phosphoproteins
  • Pxn protein, mouse
  • Receptors for Activated C Kinase
  • peptide I
  • Tyrosine
  • Protein-Tyrosine Kinases
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Oncogene Protein pp60(v-src)
  • Ptk2 protein, mouse
  • Protein Kinase C