Zhenjia Yu1, Zhen Li1, Chenchen Wang2, Tao Pan1, Xinyu Chang1, Xiaofeng Wang3, Quan Zhou1, Xiongyan Wu1, Jianfang Li1, Jinping Zhang4, Bingya Liu1, Zhenggang Zhu5, Liping Su6. 1. Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. 2. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China. 3. Department of General Surgery, First People's Hospital, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China. 4. Institute of Biology and Medical Sciences, Soochow University, Suzhou, 215123, Jiangsu, China. 5. Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. zzg1954@hotmail.com. 6. Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. suliping@shsmu.edu.cn.
Abstract
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.
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.
Entities:
Keywords:
Gastric cancer; Metastasis; Oncostatin M; Tumorigenesis
Authors: M Kortylewski; P C Heinrich; A Mackiewicz; U Schniertshauer; U Klingmüller; K Nakajima; T Hirano; F Horn; I Behrmann Journal: Oncogene Date: 1999-06-24 Impact factor: 9.867