Psoriasin (S100A7) associates with integrin beta 6 subunit and is required for alpha v beta 6-dependent carcinoma cell invasion

• Published in: Oncogene Vol. 30; no. 12; pp. 1422 - 1435
• Main Authors: Morgan, M R, Jazayeri, M, Ramsay, A G, Thomas, G J, Boulanger, M J, Hart, I R, Marshall, J F
• Format: Journal Article
• Language: English
• Published: 24-03-2011
• ISSN: 0950-9232
• DOI: 10.1038/onc.2010.535

Expression of the integrin alpha v beta 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 alpha v beta 6 composed of wild-type alpha v and a mutant beta 6 that lacks the unique C-terminal 11 amino acids (aa). We found that these residues, although not required for alpha v beta 6-dependent adhesion or migration, are essential for alpha v beta 6-dependent invasive activity. We have used a proteomic approach to identify novel binding partners for the beta 6 subunit cytoplasmic tail and report that psoriasin (Psor) (S100A7) bound preferentially to the recombinant beta 6 cytoplasmic domain, though not in the absence of the unique C-terminal 11aa. Endogenous cellular Psor co-precipitated with endogenous beta 6 and colocalised with alpha v beta 6 at the cell membrane and intracellular vesicles. Knockdown of Psor, with small interfering RNA, had no effect on alpha v beta 6-dependent adhesion or migration but abrogated alpha v beta 6-mediated oral carcinoma cell invasion both in Transwell and, the more physiologically relevant, organotypic invasion assays, recapitulating the behaviour of the beta 6-mutant cell line. Membrane-permeant Tat-peptides encoding the unique C-terminal residues of beta 6, bound directly to recombinant Psor and inhibited cellular Psor binding to beta 6; this blocked alpha v beta 6-dependent, but not alpha v beta 6-independent, invasion. These data identify a novel interaction between Psor and beta 6 and demonstrate that it is required for alpha v beta 6-dependent invasion by carcinoma cells. Inhibition of this interaction may represent a novel therapeutic strategy to target carcinoma invasion.