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

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 p...

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Main Authors: John C Dawson, Susann Bruche, Heather J Spence, Vania M M Braga, Laura M Machesky
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0031141&type=printable
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author John C Dawson
Susann Bruche
Heather J Spence
Vania M M Braga
Laura M Machesky
author_facet John C Dawson
Susann Bruche
Heather J Spence
Vania M M Braga
Laura M Machesky
author_sort John C Dawson
collection DOAJ
description 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.
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spelling doaj-art-a5e57de7038d49d480ef17bb33be33eb2025-08-20T03:09:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0173e3114110.1371/journal.pone.0031141Mtss1 promotes cell-cell junction assembly and stability through the small GTPase Rac1.John C DawsonSusann BrucheHeather J SpenceVania M M BragaLaura M MacheskyCell-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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0031141&type=printable
spellingShingle John C Dawson
Susann Bruche
Heather J Spence
Vania M M Braga
Laura M Machesky
Mtss1 promotes cell-cell junction assembly and stability through the small GTPase Rac1.
PLoS ONE
title Mtss1 promotes cell-cell junction assembly and stability through the small GTPase Rac1.
title_full Mtss1 promotes cell-cell junction assembly and stability through the small GTPase Rac1.
title_fullStr Mtss1 promotes cell-cell junction assembly and stability through the small GTPase Rac1.
title_full_unstemmed Mtss1 promotes cell-cell junction assembly and stability through the small GTPase Rac1.
title_short Mtss1 promotes cell-cell junction assembly and stability through the small GTPase Rac1.
title_sort mtss1 promotes cell cell junction assembly and stability through the small gtpase rac1
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0031141&type=printable
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