Oncostatin M receptor is a novel therapeutic target in cervical squamous cell carcinoma.
Bottom Line: An exciting new molecular target for the treatment of cervical squamous cell carcinoma (SCC), and possibly for SCCs at other anatomical sites, is the oncostatin M receptor (OSMR).This cell surface cytokine receptor is commonly copy number gained and overexpressed in advanced cervical SCC, changes that are associated with significantly worse clinical outcomes.OSMR overexpression in cervical SCC cells results in enhanced responsiveness to the major ligand oncostatin M (OSM), which induces several pro-malignant effects, including a pro-angiogenic phenotype and increased cell migration and invasiveness.
Affiliation: Department of Pathology, University of Cambridge, UK.Show MeSH
Related in: MedlinePlus
Mentions: Our group has studied the biological basis of the association between OSMR overexpression and adverse clinical outcome in cervical SCC. In representative OSMR-overexpressing cervical SCC cell lines, OSM activated (ie phosphorylated) STAT3, p44/42 MAPK, and S6 ribosomal protein, effects that were reduced after OSMR depletion using RNA interference (Figure 1) 5. These observations were in agreement with data suggesting that STAT3 is the main STAT transcription factor activated by OSM–OSMR in transformed and non-transformed cells 22. We next studied the effects of OSM–OSMR interactions on the phenotype of cervical SCC cells by using complementary in vitro approaches including gene depletion and overexpression 18. By comparing cell lines that overexpressed OSMR with those showing no OSMR overexpression, we concluded that OSMR up-regulation conferred increased sensitivity to OSM, which induced a pro-malignant phenotype, via both direct and indirect effects.
Affiliation: Department of Pathology, University of Cambridge, UK.