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Gastric Cancer

, Volume 22, Issue 5, pp 955–966 | Cite as

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

  • Zhenjia Yu
  • Zhen Li
  • Chenchen Wang
  • Tao Pan
  • Xinyu Chang
  • Xiaofeng Wang
  • Quan Zhou
  • Xiongyan Wu
  • Jianfang Li
  • Jinping Zhang
  • Bingya Liu
  • Zhenggang ZhuEmail author
  • Liping SuEmail author
Original Article
  • 241 Downloads

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.

Keywords

Oncostatin M Gastric cancer Tumorigenesis Metastasis 

Notes

Acknowledgements

We thank LetPub (http://www.letpub.com) for the linguistic assistance during the preparation of this manuscript. This research was funded by National Natural Scientific Funding of China [Nos. 81572798, 81672822, 81871902 and 81871904] and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support [20152505].

Supplementary material

10120_2019_934_MOESM1_ESM.docx (234 kb)
Supplementary material 1 (DOCX 234 KB)

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Copyright information

© The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2019

Authors and Affiliations

  1. 1.Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Department of SurgeryRuijin Hospital, Shanghai Jiao Tong University School of MedicineShanghaiChina
  2. 2.State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
  3. 3.Department of General Surgery, First People’s HospitalShanghai General Hospital, Shanghai Jiao Tong University School of MedicineShanghaiChina
  4. 4.Institute of Biology and Medical SciencesSoochow UniversitySuzhouChina

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