Oncostatin M receptor, positively regulated by SP1, promotes gastric cancer growth and metastasis upon treatment with Oncostatin M

Background Oncostatin M receptor (OSMR) is a member of the interleukin 6 (IL-6) receptor family that transduces signaling events of Oncostatin M (OSM). OSM–OSMR signaling plays a key role in inflammation and cancer progression. However, the role of OSM–OSMR in gastric cancer (GC) is still unknown. Methods OSMR expression in GC was determined by real-time PCR (RT-PCR), immunohistochemistry (IHC) and Western blot. The effects of OSM–OSMR on GC cell proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) in vitro and metastasis in vivo were examined. The pathways underlying OSM–OSMR signaling were explored by Western blot. Regulatory mechanism between SP1 and OSMR was explored in vitro. Results OSMR was highly expressed in GC tissues and its expression level was closely associated with age, T stage, Lauren classification, lymph node metastasis, TNM stage and worse prognosis of patients with GC. Knockdown of OSMR expression in GC cells significantly inhibited cell proliferation, migration, invasion, and EMT in vitro, as well as tumorigenesis and peritoneal metastasis in vivo induced by OSM. These effects mediated by OSM–OSMR were dependent on the activation of STAT3/FAK/Src signaling. SP1 could bind to the promoter region of human OSMR gene from − 255 to − 246 bp, and transcriptionally regulated OSMR overexpression in GC cells. Conclusions OSM–OSMR contributes to GC progression through activating STAT3/FAK/Src signaling, and OSMR is transcriptionally activated by SP1.