p63RhoGEF-mediated formation of a single polarized lamellipodium is required for chemotactic migration in breast carcinoma cells

FEBS Lett. 2013 Mar 18;587(6):698-705. doi: 10.1016/j.febslet.2013.01.043. Epub 2013 Feb 1.

Abstract

Short hairpin RNAs targeting 66 Rho-GEFs were screened for inhibition of chemotaxis. Six Rho-GEFs (p63RhoGEF, Trio, Duet, Net1, Frabin/Fgd4, and AAH33666) were found to be required for the serum-induced chemotactic migration of MDA-MB-231 human breast carcinoma cells. Knockdown of p63RhoGEF suppressed serum-induced RhoA activation and chemotaxis and caused the aberrant formation of multiple lamellipodial protrusions after serum stimulation while control cells formed a single polarized lamellipodium. These results indicate that p63RhoGEF plays a crucial role in serum-induced chemotaxis by limiting lamellipodial protrusion to one direction via RhoA activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Carcinoma / genetics*
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Cell Line, Tumor
  • Chemotaxis / genetics*
  • Female
  • Gene Expression
  • Guanine Nucleotide Exchange Factors / antagonists & inhibitors
  • Guanine Nucleotide Exchange Factors / genetics*
  • Guanine Nucleotide Exchange Factors / metabolism
  • High-Throughput Screening Assays
  • Humans
  • Plasmids
  • Pseudopodia / genetics*
  • Pseudopodia / metabolism
  • Pseudopodia / pathology
  • RNA, Small Interfering / genetics*
  • Rho Guanine Nucleotide Exchange Factors
  • Serum / chemistry
  • Transfection

Substances

  • ARHGEF25 protein, human
  • Guanine Nucleotide Exchange Factors
  • RNA, Small Interfering
  • Rho Guanine Nucleotide Exchange Factors