Abstract |
R-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.
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Authors | Tabetha M Bonacci, Dianne S Hirsch, Yi Shen, Milos Dokmanovic, Wen Jin Wu |
Journal | Cellular signalling
(Cell Signal)
Vol. 24
Issue 11
Pg. 2102-10
(Nov 2012)
ISSN: 1873-3913 [Electronic] England |
PMID | 22820501
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)
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Copyright | Published by Elsevier Inc. |
Chemical References |
- Adaptor Proteins, Signal Transducing
- Cadherins
- DIAPH1 protein, human
- Formins
- Profilins
- R-cadherin
- RNA, Small Interfering
- ErbB Receptors
- rho GTP-Binding Proteins
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Topics |
- Adaptor Proteins, Signal Transducing
(antagonists & inhibitors, genetics, metabolism)
- Cadherins
(antagonists & inhibitors, genetics, metabolism)
- Cell Line, Tumor
- ErbB Receptors
(metabolism)
- Formins
- Humans
- Profilins
(antagonists & inhibitors, genetics, metabolism)
- RNA Interference
- RNA, Small Interfering
(metabolism)
- Signal Transduction
- Up-Regulation
- rho GTP-Binding Proteins
(metabolism)
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