Oncotarget

Research Papers:

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

Victoria Casado-Medrano, Laura Barrio-Real, Ginesa García-Rostán, Matti Baumann, Oliver Rocks and María J. Caloca _

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Oncotarget. 2016; 7:28301-28319. https://doi.org/10.18632/oncotarget.8597

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Abstract

Victoria Casado-Medrano1, Laura Barrio-Real2, Ginesa García-Rostán1, Matti Baumann3, Oliver Rocks3 , María J. Caloca1

1Instituto de Biología y Genética Molecular (IBGM), Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Valladolid, 47003 Valladolid, Spain

2Current address: Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

3Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany

Correspondence to:

María J. Caloca, email: mj.caloca@csic.es

Keywords: β2-chimaerin, breast cancer, E-cadherin, metastasis, Rac1

Received: February 15, 2016     Accepted: March 27, 2016     Published: April 5, 2016

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.


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