Knockdown of Hop downregulates RhoC expression, and decreases pseudopodia formation and migration in cancer cell lines

Cancer Lett. 2013 Jan 28;328(2):252-60. doi: 10.1016/j.canlet.2012.09.021. Epub 2012 Oct 2.

Abstract

The Hsp90/Hsp70 organising protein (Hop) is a co-chaperone that mediates the interaction of Hsp90 and Hsp70 molecular chaperones during assembly of Hsp90 complexes in cells. Formation of Hsp90 complexes is a key intermediate step in the maturation and homeostasis of oncoproteins and several hormone receptors. In this paper, we demonstrate that knockdown of Hop decreased migration of Hs578T and MDA-MB-231 breast cancer cells. Hop was identified in isolated pseudopodia fractions; it colocalised with actin in lamellipodia, and co-sedimented with purified actin in vitro. Knockdown of Hop caused a decrease in the level of RhoC GTPase, and significantly inhibited pseudopodia formation in Hs578T cells. Our data suggest that Hop regulates directional cell migration by multiple unknown mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Protein Transport
  • Pseudopodia / genetics*
  • Pseudopodia / metabolism
  • RNA Interference
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism
  • rho GTP-Binding Proteins / genetics*
  • rho GTP-Binding Proteins / metabolism
  • rhoC GTP-Binding Protein

Substances

  • Actins
  • HOPX protein, human
  • Homeodomain Proteins
  • Tumor Suppressor Proteins
  • RHOC protein, human
  • rho GTP-Binding Proteins
  • rhoC GTP-Binding Protein