Estradiol-Induced Epithelial to Mesenchymal Transition and Migration Are Inhibited by Blocking c-Src Kinase in Breast Cancer Cell Lines
- Author:
Javier E. JIMÉNEZ-SALAZAR
1
;
Rene M. RIVERA-ESCOBAR
;
Rebeca DAMIÁN-FERRARA
;
Juan MALDONADO-CUBAS
;
Catalina RINCÓN-PÉREZ
;
Rosario TARRAGÓ-CASTELLANOS
;
Pablo DAMIÁN-MATSUMURA
Author Information
- Publication Type:Original Article
- From:Journal of Breast Cancer 2023;26(5):446-460
- CountryRepublic of Korea
- Language:English
-
Abstract:
Purpose:The epithelial-to-mesenchymal transition (EMT) is the main event that favors cell migration and metastasis in breast cancer. Previously, we demonstrated that 1 nM estradiol (E2 ) promotes EMT, induced by c-Src kinase, causing changes in the localization of proteins that compose the tight junction (TJ) and adherens junction (AJ).
Methods:The present work highlights the central role of c-Src in the initiation of metastasis, induced by E2 , through increasing the ability of MCF-7 and T47-D cells, which express estrogen receptor alpha (ERα), to migrate and invade before they become metastatic.
Results:Treatment with E2 can activate two signaling pathways, the first one by the phosphorylated c-Src (p-Src) which forms the p-Src/E-cadherin complex. This phenomenon was completely prevented by incubation with a selective inhibitor of c-Src (5 µM PP2).p-Src then promotes the downregulation of E-cadherin and occludin, which are epithelial phenotype marker proteins of the AJ and TJ, respectively. In the second pathway, E2 binds to ERα, creating a complex that translocates to the nucleus, inducing the synthesis of SNAIL1 and N-cadherin proteins, markers of the mesenchymal phenotype. Both processes increased the migratory and invasive capacities of both cell lines.
Conclusion:The present study demonstrate that E2 enhance EMT and migration, through c-Src activation, in human breast cancer cells that express ERα and become potential therapeutic targets.
