Tissue transglutaminase mediates the pro-malignant effects of oncostatin M receptor over-expression in cervical squamous cell carcinoma.
Bottom Line: Cervical SCC cells that over-express OSMR show enhanced responsiveness to the major ligand OSM, which induces multiple pro-malignant effects, including increased cell migration and invasiveness.Here, we show that tissue transglutaminase (TGM2) is an important mediator of the ligand-dependent phenotypic effects of OSMR over-expression in SCC cells.We conclude that an OSMR/TGM2/integrin-α5β1/fibronectin pathway is of biological significance in cervical SCC and a candidate for therapeutic targeting.
Affiliation: Department of Pathology, University of Cambridge, UK.Show MeSH
Related in: MedlinePlus
Mentions: By interrogating published datasets (sets 3 and 5), we found that integrin–α5β1 and fibronectin were significantly over-expressed in cervical and oral SCCs and that levels of integrin–β1 and fibronectin correlated with those of OSMR and TGM2 (Figure 5). These correlations were validated in our independent dataset of cervical SCCs (set 1), where integrin–α5 levels were also associated with OSMR expression (see Supplementary material, Figure S7, Table S3). In an independent dataset of oral SCCs (set 6), levels of integrin–α5β1 and fibronectin again correlated with those of OSMR, while integrin–α5 and fibronectin levels correlated with TGM2 expression (see Supplementary material, Figure S7).
Affiliation: Department of Pathology, University of Cambridge, UK.