title: Mtss1 promotes cell-cell junction assembly and stability through the small GTPase Rac1.
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.
authors.affiliation: Beatson Institute for Cancer Research, Glasgow, United Kingdom. john.c.dawson@ed.ac.uk
authors.forename: John C
authors.initials: JC
authors.lastname: Dawson
authors.forename: Susann
authors.initials: S
authors.lastname: Bruche
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Spence
authors.forename: Vania M M
authors.initials: VM
authors.lastname: Braga
authors.forename: Laura M
authors.initials: LM
authors.lastname: Machesky
mesh_terms: D000199:Actins / Q000378:metabolism; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D031541:Fluorescence Resonance Energy Transfer; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D014162:Transfection; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000199:Actins; D015820:Cadherins; C486778:MTSS1 protein, human; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D049452:Green Fluorescent Proteins; D017228:Hepatocyte Growth Factor; D020830:rac1 GTP-Binding Protein