Mtss1 promotes cell-cell junction assembly and stability through the small GTPase Rac1

Dawson, J.C., Bruche, S., Spence, H.J., Braga, V.M.M. and Machesky, L.M. (2012) Mtss1 promotes cell-cell junction assembly and stability through the small GTPase Rac1. PLoS ONE, 7(3), e31141. (doi: 10.1371/journal.pone.0031141) (PMID:22479308) (PMCID:PMC3313965)

Abstract

Cell-cell junctions are an integral part of epithelia and are often disrupted in cancer cells during epithelial-to-mesenchymal transition (EMT), which is a main driver of metastatic spread. We show here that Metastasis suppressor-1 (Mtss1; Missing in Metastasis, MIM), a member of the IMD-family of proteins, inhibits cell-cell junction disassembly in wound healing or HGF-induced scatter assays by enhancing cell-cell junction strength. Mtss1 not only makes cells more resistant to cell-cell junction disassembly, but also accelerates the kinetics of adherens junction assembly. Mtss1 drives enhanced junction formation specifically by elevating Rac-GTP. Lastly, we show that Mtss1 depletion reduces recruitment of F-actin at cell-cell junctions. We thus propose that Mtss1 promotes Rac1 activation and actin recruitment driving junction maintenance. We suggest that the observed loss of Mtss1 in cancers may compromise junction stability and thus promote EMT and metastasis.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Machesky, Professor Laura
• Authors: Dawson, J.C., Bruche, S., Spence, H.J., Braga, V.M.M., and Machesky, L.M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: PLoS ONE
• Publisher: Public Library of Science
• ISSN: 1932-6203
• Published Online: 27 March 2012
• Copyright Holders: Copyright © 2012 The Authors
• First Published: First published in PLoS ONE 7(3):e31141
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher