Role of ARHGAP24 in ADP Ribosylation Factor 6 (ARF6)-dependent Pseudopod Formation in Human Breast Carcinoma Cells

Anticancer Res. 2017 Sep;37(9):4837-4844. doi: 10.21873/anticanres.11891.

Abstract

Background/aim: The small GTPase ADP ribosylation factor 6 (ARF6) promotes carcinoma cell invasion and metastasis through remodeling of actin cytoskeleton and formation of pseudopod that is regulated by RAC. RHO GTPase activating protein 24 (ARHGAP24), a RAC-specific GTPase activating protein, binds to activated ARF6 and is recruited to the plasma membrane. The aim of the present study was to demonstrate if ARHGAP24 is involved in the ARF6-mediated formation of pseudopods in breast carcinoma cells.

Materials and methods: The formation of pseudopods induced by activated ARF6 was monitored using MDA-MB-231 human breast carcinoma cells. The effect of knockdown of endogenous ARHGAP24 by siRNA was examined.

Results: Knockdown of ARHGAP24 in MDA-MB-231 carcinoma cells increased the lifespan of pseudopods to retract, which resulted in increased length of pseudopods induced by activated ARF6. ARHGAP24 required a binding site of ARF6 to achieve ARF6-dependent actin remodeling.

Conclusion: ARHGAP24 may regulate pseudopod formation downstream of activated ARF6 in MDA-MB-231 human breast carcinoma cells.

Keywords: Breast cancer; actin cytoskeleton; cancer cell migration; small GTPases.

MeSH terms

  • ADP-Ribosylation Factor 6
  • ADP-Ribosylation Factors / metabolism*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Shape
  • Extracellular Matrix / metabolism
  • Female
  • GTPase-Activating Proteins / chemistry
  • GTPase-Activating Proteins / metabolism*
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Protein Binding
  • Protein Domains
  • Pseudopodia / metabolism*

Substances

  • ADP-Ribosylation Factor 6
  • ARHGAP24 protein, human
  • GTPase-Activating Proteins
  • ADP-Ribosylation Factors
  • ARF6 protein, human