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Original article
Gastrokine 1 induces senescence through p16/Rb pathway activation in gastric cancer cells
  1. Rui Xing1,
  2. Wenmei Li2,
  3. Jiantao Cui2,
  4. Jun Zhang1,
  5. Bin Kang1,
  6. Yuan Wang1,
  7. Zhaohui Wang1,
  8. Siqi Liu1,
  9. Youyong Lu1,2
  1. 1Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
  2. 2Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University School of Oncology, Beijing Cancer Hospital/Institute, Beijing, China
  1. Correspondence to Dr Youyong Lu, Peking University School of Oncology, Beijing Cancer Hospital/Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; youyonglu{at}hsc.pku.edu.cn Dr Siqi Liu, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing Airport Industrial Zone B-6, Shunyi District, Beijing 101318, China; siqiliu{at}genomics.org.cn

Abstract

Background and aims Gastrokine 1 (GKN1) is a stomach-specific protein that is normally expressed in gastric mucosa but not in primary tumours and cell lines. Based on this evidence, it was presumed that GKN1 might play a role in gastric cancer development; however, its function and molecular mechanism are not clear. A systematic study was initiated that combined multiple approaches to define the molecular mechanism of GKN1 in gastric cancer cells.

Method Proteomics, western blotting and immunohistochemistry were used to measure the expression level of GKN1. Western blotting combined with immunofluorescence was used to monitor the secretory process of this protein. Subsequently, the function and molecular mechanism of GKN1 was explored in vitro and in vivo.

Results It was shown that GKN1 is an autocrine/paracrine protein and inhibits cell growth due to senescence, which resulted from activation of p16/Rb and p21waf pathways. Furthermore, sustained activation of Ras/Raf/MEK/ERK signalling was characterised in gastric cancer cells and a xenograft nude mouse model following GKN1 treatment.

Conclusion These results provide comprehensive molecular evidence of GKN1 in inducing senescence of gastric cancer cells, and indicate that GKN1 might be a potential novel target for gastric cancer therapeutics.

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Footnotes

  • Siqi Liu and Youyong Lu are co-corresponding authors.

  • Funding This work was supported by the National Bio-Tech 86-3 (2006AA02A402), 97-3 program (2009CB522204) and Science and Technology Project of Beijing, China (D0905001040332).

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Institutional Ethical Standards Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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