| First Author | Casado-Medrano V | Year | 2016 |
| Journal | Oncotarget | Volume | 7 |
| Issue | 19 | Pages | 28301-19 |
| PubMed ID | 27058424 | Mgi Jnum | J:263350 |
| Mgi Id | MGI:6161938 | Doi | 10.18632/oncotarget.8597 |
| Citation | Casado-Medrano V, et al. (2016) A new role of the Rac-GAP beta2-chimaerin in cell adhesion reveals opposite functions in breast cancer initiation and tumor progression. Oncotarget 7(19):28301-19 |
| abstractText | beta2-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 beta2-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 beta2-chimaerin in breast cancer epithelial cells reduces E-cadherin protein levels, thus loosening cell-cell contacts. In vivo, genetic ablation of beta2-chimaerin in the MMTV-Neu/ErbB2 mice accelerates tumor onset, but delays tumor progression. Finally, analysis of clinical databases revealed an inverse correlation between beta2-chimaerin and E-cadherin gene expressions in Her2+ breast tumors. Furthermore, breast cancer patients with low beta2-chimaerin expression have reduced relapse free survival but develop metastasis at similar times. Overall, our data redefine the role of beta2-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. |
