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dc.contributor.authorRabinovitz, Isaac
dc.contributor.authorToker, Alex
dc.contributor.authorMercurio, Arthur M.
dc.date2022-08-11T08:08:01.000
dc.date.accessioned2022-08-23T15:39:43Z
dc.date.available2022-08-23T15:39:43Z
dc.date.issued1999-09-09
dc.date.submitted2010-11-07
dc.identifier.citationJ Cell Biol. 1999 Sep 6;146(5):1147-60. <a href="http://dx.doi.org/10.1300/J186v05n03_09">Link to article on publisher's website</a>
dc.identifier.issn0021-9525 (Linking)
dc.identifier.doi10.1300/J186v05n03_09
dc.identifier.pmid10477766
dc.identifier.urihttp://hdl.handle.net/20.500.14038/26238
dc.description.abstractWe explored the hypothesis that the chemotactic migration of carcinoma cells that assemble hemidesmosomes involves the activation of a signaling pathway that releases the alpha6beta4 integrin from these stable adhesion complexes and promotes its association with F-actin in cell protrusions enabling it to function in migration. Squamous carcinoma-derived A431 cells were used because they express alpha6beta4 and migrate in response to EGF stimulation. Using function-blocking antibodies, we show that the alpha6beta4 integrin participates in EGF-stimulated chemotaxis and is required for lamellae formation on laminin-1. At concentrations of EGF that stimulate A431 chemotaxis ( approximately 1 ng/ml), the alpha6beta4 integrin is mobilized from hemidesmosomes as evidenced by indirect immunofluorescence microscopy using mAbs specific for this integrin and hemidesmosomal components and its loss from a cytokeratin fraction obtained by detergent extraction. EGF stimulation also increased the formation of lamellipodia and membrane ruffles that contained alpha6beta4 in association with F-actin. Importantly, we demonstrate that this mobilization of alpha6beta4 from hemidesmosomes and its redistribution to cell protrusions occurs by a mechanism that involves activation of protein kinase C-alpha and that it is associated with the phosphorylation of the beta4 integrin subunit on serine residues. Thus, the chemotactic migration of A431 cells on laminin-1 requires not only the formation of F-actin-rich cell protrusions that mediate alpha6beta4-dependent cell movement but also the disruption of alpha6beta4-containing hemidesmosomes by protein kinase C.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=10477766&dopt=Abstract">Link to Article in PubMed</a>
dc.subjectActins
dc.subjectAntigens, Surface
dc.subjectCarbazoles
dc.subjectCarcinoma, Squamous Cell
dc.subjectCell Membrane
dc.subjectCell Size
dc.subject*Chemotaxis
dc.subjectDesmosomes
dc.subjectEnzyme Activation
dc.subjectEpidermal Growth Factor
dc.subjectHumans
dc.subjectIndoles
dc.subjectIntegrin alpha6beta4
dc.subjectIntegrins
dc.subjectKeratins
dc.subjectLaminin
dc.subjectPhosphorylation
dc.subjectPhosphoserine
dc.subjectPhosphotyrosine
dc.subjectProtein Kinase C
dc.subjectPseudopodia
dc.subjectReceptor, Epidermal Growth Factor
dc.subjectSignal Transduction
dc.subjectTumor Cells, Cultured
dc.subjectCancer Biology
dc.subjectNeoplasms
dc.titleProtein kinase C-dependent mobilization of the alpha6beta4 integrin from hemidesmosomes and its association with actin-rich cell protrusions drive the chemotactic migration of carcinoma cells
dc.typeArticle
dc.source.journaltitleThe Journal of cell biology
dc.source.volume146
dc.source.issue5
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1152&amp;context=cancerbiology_pp&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/cancerbiology_pp/152
dc.identifier.contextkey1633377
refterms.dateFOA2022-08-23T15:39:43Z
html.description.abstract<p>We explored the hypothesis that the chemotactic migration of carcinoma cells that assemble hemidesmosomes involves the activation of a signaling pathway that releases the alpha6beta4 integrin from these stable adhesion complexes and promotes its association with F-actin in cell protrusions enabling it to function in migration. Squamous carcinoma-derived A431 cells were used because they express alpha6beta4 and migrate in response to EGF stimulation. Using function-blocking antibodies, we show that the alpha6beta4 integrin participates in EGF-stimulated chemotaxis and is required for lamellae formation on laminin-1. At concentrations of EGF that stimulate A431 chemotaxis ( approximately 1 ng/ml), the alpha6beta4 integrin is mobilized from hemidesmosomes as evidenced by indirect immunofluorescence microscopy using mAbs specific for this integrin and hemidesmosomal components and its loss from a cytokeratin fraction obtained by detergent extraction. EGF stimulation also increased the formation of lamellipodia and membrane ruffles that contained alpha6beta4 in association with F-actin. Importantly, we demonstrate that this mobilization of alpha6beta4 from hemidesmosomes and its redistribution to cell protrusions occurs by a mechanism that involves activation of protein kinase C-alpha and that it is associated with the phosphorylation of the beta4 integrin subunit on serine residues. Thus, the chemotactic migration of A431 cells on laminin-1 requires not only the formation of F-actin-rich cell protrusions that mediate alpha6beta4-dependent cell movement but also the disruption of alpha6beta4-containing hemidesmosomes by protein kinase C.</p>
dc.identifier.submissionpathcancerbiology_pp/152
dc.contributor.departmentDepartment of Cancer Biology
dc.source.pages1147-60


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