A new role of the Rac-GAP β2-chimaerin in cell adhesion reveals opposite functions in breast cancer initiation and tumor progression
| Autor: | Oliver Rocks, María J. Caloca, Victoria Casado-Medrano, Ginesa Garcia-Rostan, Laura Barrio-Real, Matti Baumann |
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| Přispěvatelé: | Ministerio de Economía y Competitividad (España), Junta de Castilla y León |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Cancer Research β2-chimaerin Breast Neoplasms RAC1 Tumor initiation Metastasis Mice 03 medical and health sciences breast cancer 0302 clinical medicine Breast cancer Cell Adhesion medicine Animals Humans metastasis Cell adhesion skin and connective tissue diseases Mice Knockout Cadherin business.industry E-cadherin medicine.disease Molecular medicine Neoplasm Proteins Cell Transformation Neoplastic 030104 developmental biology Oncology Tumor progression 030220 oncology & carcinogenesis Disease Progression MCF-7 Cells Cancer research Female business Rac1 Research Paper |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Oncotarget |
| Popis: | 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. This work was initially supported by a grant from the Spanish Ministry of Economy and Competitiveness to MJC (BFU2009-08051), but could be finished only thanks to the support from the Castilla-León Autonomous Government to MJC (grants BIO103/VA44/11, BIO/VA22/14, CSI090U14 and BIO/VA34/15). |
| Databáze: | OpenAIRE |
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