title: Gastrokine 1 induces senescence through p16/Rb pathway activation in gastric cancer cells.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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 p21(waf) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xing
authors.forename: Wenmei
authors.initials: W
authors.lastname: Li
authors.forename: Jiantao
authors.initials: J
authors.lastname: Cui
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Kang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Wang
authors.forename: Siqi
authors.initials: S
authors.lastname: Liu
authors.forename: Youyong
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000502:physiology; D005455:Fluorescent Antibody Technique; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D036361:Peptide Hormones / Q000378:metabolism* / Q000502:physiology; D040901:Proteomics; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D013274:Stomach Neoplasms / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: D015415:Biomarkers; C477000:GKN1 protein, human; D036361:Peptide Hormones