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Small GTPase Rho regulates R-cadherin through Dia1/profilin-1.

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.
AuthorsTabetha M Bonacci, Dianne S Hirsch, Yi Shen, Milos Dokmanovic, Wen Jin Wu
JournalCellular signalling (Cell Signal) Vol. 24 Issue 11 Pg. 2102-10 (Nov 2012) ISSN: 1873-3913 [Electronic] England
PMID22820501 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)
CopyrightPublished 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
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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