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dc.contributor.authorRabinovitz, Isaac
dc.contributor.authorGipson, I. K.
dc.contributor.authorMercurio, Arthur M.
dc.date2022-08-11T08:08:01.000
dc.date.accessioned2022-08-23T15:39:45Z
dc.date.available2022-08-23T15:39:45Z
dc.date.issued2001-12-12
dc.date.submitted2010-11-07
dc.identifier.citation<p>Mol Biol Cell. 2001 Dec;12(12):4030-43.</p>
dc.identifier.issn1059-1524 (Linking)
dc.identifier.doi10.1091/mbc.12.12.4030
dc.identifier.pmid11739798
dc.identifier.urihttp://hdl.handle.net/20.500.14038/26244
dc.description.abstractThe integrin alpha6beta4, a laminin receptor that stabilizes epithelial cell adhesion to the basement membrane (BM) through its association with cytokeratins, can stimulate the formation and stabilization of actin-rich protrusions in carcinoma cells. An important, unresolved issue, however, is whether this integrin can transmit forces to the substrate generated by the acto-myosin system. Using a traction-force detection assay, we detected forces exerted through alpha6beta4 on either laminin-1 or on an anti-alpha6 antibody, demonstrating that this integrin can transmit forces without the need to engage other integrins. These alpha6beta4-dependent traction forces were organized into a compression machine localized to the base of lamellae. We hypothesized that the compression forces generated by alpha6beta4 result in the remodeling of BMs because this integrin plays a major role in the interaction of epithelial and carcinoma cells with such structures. Indeed, we observed that carcinoma cells are able to remodel a reconstituted BM through alpha6beta4-mediated compression forces by a process that involves the packing of BM material under the cells and the mechanical removal of BM from adjacent areas. The distinct signaling functions of alpha6beta4, which activate phosphoinositide 3-OH kinase and RhoA, also contribute to remodeling. Importantly, we demonstrate remodeling of a native BM by epithelial cells and the involvement of alpha6beta4 in this remodeling. Our findings have important implications for the mechanism of both BM organization and tumor invasion.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=11739798&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC60773
dc.subjectAntigens, Surface
dc.subjectBasement Membrane
dc.subjectBreast Neoplasms
dc.subjectCell Adhesion
dc.subjectExtracellular Matrix
dc.subjectHumans
dc.subjectIntegrin alpha6beta4
dc.subjectIntegrins
dc.subjectLaminin
dc.subjectMicroscopy, Electron
dc.subjectMicroscopy, Fluorescence
dc.subjectMicroscopy, Video
dc.subject*Neoplasm Invasiveness
dc.subjectNeoplasms
dc.subjectPseudopodia
dc.subjectSignal Transduction
dc.subjectTumor Cells, Cultured
dc.subjectCancer Biology
dc.subjectNeoplasms
dc.titleTraction forces mediated by alpha6beta4 integrin: implications for basement membrane organization and tumor invasion
dc.typeJournal Article
dc.source.journaltitleMolecular biology of the cell
dc.source.volume12
dc.source.issue12
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/cancerbiology_pp/158
dc.identifier.contextkey1633383
html.description.abstract<p>The integrin alpha6beta4, a laminin receptor that stabilizes epithelial cell adhesion to the basement membrane (BM) through its association with cytokeratins, can stimulate the formation and stabilization of actin-rich protrusions in carcinoma cells. An important, unresolved issue, however, is whether this integrin can transmit forces to the substrate generated by the acto-myosin system. Using a traction-force detection assay, we detected forces exerted through alpha6beta4 on either laminin-1 or on an anti-alpha6 antibody, demonstrating that this integrin can transmit forces without the need to engage other integrins. These alpha6beta4-dependent traction forces were organized into a compression machine localized to the base of lamellae. We hypothesized that the compression forces generated by alpha6beta4 result in the remodeling of BMs because this integrin plays a major role in the interaction of epithelial and carcinoma cells with such structures. Indeed, we observed that carcinoma cells are able to remodel a reconstituted BM through alpha6beta4-mediated compression forces by a process that involves the packing of BM material under the cells and the mechanical removal of BM from adjacent areas. The distinct signaling functions of alpha6beta4, which activate phosphoinositide 3-OH kinase and RhoA, also contribute to remodeling. Importantly, we demonstrate remodeling of a native BM by epithelial cells and the involvement of alpha6beta4 in this remodeling. Our findings have important implications for the mechanism of both BM organization and tumor invasion.</p>
dc.identifier.submissionpathcancerbiology_pp/158
dc.contributor.departmentDepartment of Cancer Biology
dc.source.pages4030-43


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