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 flow cytometry, we observed that OSM treatment significantly increased expression of integrin–α5β1 dimers at the cell surface in both SW756 and CaSki (Figure 3B). The function of TGM2 relates to its subcellular location, with cell surface protein being responsible for interactions with integrins 8. Flow cytometry demonstrated the presence of TGM2 on the cell surface of both SW756 and CaSki (Figure 4A). OSM treatment increased the levels of membrane-associated TGM2, although the differences did not reach statistical significance. Confocal microscopy confirmed the cell membrane localization of TGM2 and showed focal co-localization of TGM2 and integrin–α5 in control and OSM-treated SW756 cells grown on fibronectin (Figure 4B).
Affiliation: Department of Pathology, University of Cambridge, UK.