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

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.

• Authors: Zhenjia Yu, Zhen Li, Chenchen Wang, Tao Pan, Xinyu Chang, Xiaofeng Wang, Quan Zhou, Xiongyan Wu, Jianfang Li, Jinping Zhang, Bingya Liu, Zhenggang Zhu, Liping Su
• Journal: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association (Gastric Cancer) Vol. 22 Issue 5 Pg. 955-966 (09 2019) ISSN: 1436-3305 [Electronic] Japan
• PMID: 30778797 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Biomarkers, Tumor
• OSMR protein, human
• Oncostatin M Receptor beta Subunit
• STAT3 Transcription Factor
• Sp1 Transcription Factor
• SP1 protein, human
• Oncostatin M

Topics

• Adenocarcinoma (drug therapy, genetics, metabolism, secondary)
• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Cell Movement
• Cell Proliferation
• Female
• Follow-Up Studies
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Lymphatic Metastasis
• Male
• Mice
• Mice, Nude
• Middle Aged
• Neoplasm Invasiveness
• Oncostatin M (pharmacology)
• Oncostatin M Receptor beta Subunit (genetics, metabolism)
• Prognosis
• STAT3 Transcription Factor (genetics, metabolism)
• Signal Transduction
• Sp1 Transcription Factor (genetics, metabolism)
• Stomach Neoplasms (drug therapy, genetics, metabolism, pathology)
• Survival Rate
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays