Tabetha M Bonacci, Dianne S Hirsch, Yi Shen, Milos Dokmanovic, Wen Jin Wu
Division of Monoclonal Antibodies, Office of Biotechnology Products, Office of Pharmaceutical Science, Center for Drug Evaluation and Research, US Food and Drug Administration, Bethesda, MD 20892, USA.
Cellular signalling 2012 NovR-cadherin is a member of the classical cadherins. Though much is known about E-cadherin in adherens junction formation in epithelial cells, the role of R-cadherin in epithelial cells remains elusive. This study examines regulation of R-cadherin adherens junctions by the small GTPase Rho and its downstream effectors in MDA-MB-231 breast cancer cells, MDA-MB-231 cells stably expressing the N-terminus of c-Cbl, and MCF10A normal breast epithelial cells. We find that the small GTPase Rho regulates R-cadherin adherens junction formation via Dia1 (also known as p140mDia) and profilin-1-mediated signaling pathway. The role played by Rho in regulating R-cadherin is underscored by the fact that constitutively active RhoA(Q63L) induces R-cadherin junction formation in MDA-MB-231 cells. Importantly, R-cadherin adherens junction formation facilitates a mesenchymal to epithelial-like transition in MDA-MB-231 cells. Additionally, our data suggest an inverse relationship between EGFR signaling and R-cadherin adherens junction formation. Taken together, results from this study indicate that R-cadherin is a critical regulator of epithelial phenotype. Published by Elsevier Inc.
Tabetha M Bonacci, Dianne S Hirsch, Yi Shen, Milos Dokmanovic, Wen Jin Wu. Small GTPase Rho regulates R-cadherin through Dia1/profilin-1. Cellular signalling. 2012 Nov;24(11):2102-10
PMID: 22820501
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