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: Another of the 15 genes that were induced by OSM in OSMR-over-expressing cervical SCC cells, and also associated with OSMR over-expression in cervical SCC tissues 6, was integrin–α5 (ITGA5). As TGM2 has been reported to interact with integrin–α5β1 in mesenchymal cells, leading to binding of the cognate ligand fibronectin 23,24, we examined interactions between OSMR, TGM2, integrin–α5β1 and fibronectin in cervical SCC cells. OSM increased integrin–α5 (ITGA5), integrin–β1 (ITGB1) and fibronectin (FN1) mRNA levels in both SW756 and CaSki (see Supplementary material, Figure S2). After 48 h of OSM treatment, integrin–α5 protein levels increased 7.1- and 2.9-fold for SW756 and CaSki, respectively (Figure 3A). Integrin–β1 protein expression was also induced by OSM in CaSki, with a 1.5-fold increase at 48 h. Basal levels of integrin–β1 protein in SW756 were very high and expression did not increase further upon OSM treatment (Figure 3A). In the OSMR non-over-expressing cervical SCC cells MS751 and ME180, OSM did not induce integrin–α5 or integrin–β1 (see Supplementary material, Figure S3).
Affiliation: Department of Pathology, University of Cambridge, UK.