Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

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

[img] PDF (Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
15MB
[img]
Preview
PDF (Supplementary file) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
3MB

Item Type:Article
Title:A new role of the Rac-GAP β2-chimaerin in cell adhesion reveals opposite functions in breast cancer initiation and tumor progression
Creators Name:Casado-Medrano, V. and Barrio-Real, L. and García-Rostán, G. and Baumann, M. and Rocks, O. and Caloca, M.J.
Abstract:β2-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 β2-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 β2-chimaerin in breast cancer epithelial cells reduces E-cadherin protein levels, thus loosening cell-cell contacts. In vivo, genetic ablation of β2-chimaerin in the MMTV-Neu/ErbB2 mice accelerates tumor onset, but delays tumor progression. Finally, analysis of clinical databases revealed an inverse correlation between β2-chimaerin and E-cadherin gene expressions in Her2+ breast tumors. Furthermore, breast cancer patients with low β2-chimaerin expression have reduced relapse free survival but develop metastasis at similar times. Overall, our data redefine the role of β2-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.
Keywords:β2-Chimaerin, Breast Cancer, E-Cadherin, Metastasis, Rac1, Animals, Mice
Source:Oncotarget
ISSN:1949-2553
Publisher:Impact Journals (U.S.A.)
Volume:7
Number:19
Page Range:28301-28319
Date:10 May 2016
Official Publication:https://doi.org/10.18632/oncotarget.8597
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library