Psoriasin (S100A7) associates with integrin ?6 subunit and is required for ?v?6-dependent carcinoma cell invasion
Morgan, M.R., Jazayeri, M., Ramsey, A.G., Thomas, G.J., Boulanger, M.J, Hart, I.R. and Marshall, J.F. (2011) Psoriasin (S100A7) associates with integrin ?6 subunit and is required for ?v?6-dependent carcinoma cell invasion. Oncogene, 30, (12), 1422-1435. (doi:10.1038/onc.2010.535). (PMID:21132011).
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Expression of the integrin ?v?6 is upregulated in a variety of carcinomas where it appears to be involved in malignant progression, although the biology of this integrin is not fully explored. We have generated oral carcinoma cells that express ?v?6 composed of wild-type ?v and a mutant ?6 that lacks the unique C-terminal 11 amino acids (aa). We found that these residues, although not required for ?v?6-dependent adhesion or migration, are essential for ?v?6-dependent invasive activity. We have used a proteomic approach to identify novel binding partners for the ?6 subunit cytoplasmic tail and report that psoriasin (Psor) (S100A7) bound preferentially to the recombinant ?6 cytoplasmic domain, though not in the absence of the unique C-terminal 11aa. Endogenous cellular Psor co-precipitated with endogenous ?6 and colocalised with ?v?6 at the cell membrane and intracellular vesicles. Knockdown of Psor, with small interfering RNA, had no effect on ?v?6-dependent adhesion or migration but abrogated ?v?6-mediated oral carcinoma cell invasion both in Transwell and, the more physiologically relevant, organotypic invasion assays, recapitulating the behaviour of the ?6-mutant cell line. Membrane-permeant Tat-peptides encoding the unique C-terminal residues of ?6, bound directly to recombinant Psor and inhibited cellular Psor binding to ?6; this blocked ?v?6-dependent, but not ?v?6-independent, invasion. These data identify a novel interaction between Psor and ?6 and demonstrate that it is required for ?v?6-dependent invasion by carcinoma cells. Inhibition of this interaction may represent a novel therapeutic strategy to target carcinoma invasion.
|Digital Object Identifier (DOI):||doi:10.1038/onc.2010.535|
|Keywords:||?v?6, integrins, invasion, psoriasin, cancer, oral scc|
|Subjects:||Q Science > QH Natural history > QH426 Genetics
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
|Divisions:||Faculty of Medicine > Cancer Sciences
|Date Deposited:||29 May 2012 10:41|
|Last Modified:||31 Mar 2016 14:29|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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