MDC Lab Coats

A new role of the Rac-GAP β2-chimaerin in cell adhesion reveals opposite functions in breast cancer initiation and tumor progression

Authors

  • V. Casado-Medrano
  • L. Barrio-Real
  • G. García-Rostán
  • M. Baumann
  • O. Rocks
  • M.J. Caloca

Journal

  • Oncotarget

Citation

  • Oncotarget 7 (19): 28301-28319

Abstract

  • {beta}2-chimaerin is a Rac1-specific negative regulator and a candidate tumor suppressor in breast cancer but its precise function in mammary tumorigenesis in vivo is unknown. Here, we study for the first time the role of {beta}2-chimaerin in breast cancer using a mouse model and describe an unforeseen role for this protein in epithelial cell-cell adhesion. We demonstrate that expression of {beta}2-chimaerin in breast cancer epithelial cells reduces E-cadherin protein levels, thus loosening cell-cell contacts. In vivo, genetic ablation of {beta}2-chimaerin in the MMTV-Neu/ErbB2 mice accelerates tumor onset, but delays tumor progression. Finally, analysis of clinical databases revealed an inverse correlation between {beta}2-chimaerin and E-cadherin gene expressions in Her2+ breast tumors. Furthermore, breast cancer patients with low {beta}2-chimaerin expression have reduced relapse free survival but develop metastasis at similar times. Overall, our data redefine the role of {beta}2-chimaerin as tumor suppressor and provide the first in vivo evidence of a dual function in breast cancer, suppressing tumor initiation but favoring tumor progression.


DOI

doi:10.18632/oncotarget.8597