title: Fas Signaling Promotes Gastric Cancer Metastasis through STAT3-Dependent Upregulation of Fascin.
abstract: BACKGROUND
  Fas signaling-activated signal transducers and activators of transcription 3 (STAT3) is required for Fascin upregulation. As an actin-bundling protein, Fascin can mediate gastric cancer (GC) cell migration.
  
  
  METHODS
  Gastric cancer AGS cells were treated with anti-Fas (5 μg/ml) for 2 h, in order to stimulate the activation of the Fas signaling. The in vitro migration of Fas signaling-activated AGS cells was assessed using Transwell chambers. The levels of Fascin and phosphorylated STAT3 were detected by Western blotting analyses. Nude mice were injected intravenously with AGS cells treated with anti-Fas or treated with STAT3 inhibitor without anti-Fas; tumor pulmonary metastases were measured. Fascin protein expression in tumor tissues was detected by immunohistochemistry. The Fas and Fascin mRNA levels in tumor tissues from patients with GC were measured by real-time PCR and their correlation was analyzed.
  
  
  RESULTS
  The activation of Fas signaling promoted cell migration and resulted in STAT3-dependent Fascin upregulation in AGS cells. STAT3 enhanced Fascin levels in vivo. Fascin was the mediator of Fas signaling-induced AGS cell migration in vitro and in vivo. Furthermore, there was a positive correlation between Fas and Fascin mRNA levels in tumor tissues from GC patients.
  
  
  CONCLUSIONS
  Fas signaling promotes GC metastasis through the STAT3/Fascin pathway, which may provide a new target for GC therapy.
authors.affiliation: Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, 310022, People's Republic of China.
authors.forename: Yunshan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Hepatobiliary & Pancreatic Intervention Center, Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, People's Republic of China.
authors.forename: Qiyu
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, 310058, People's Republic of China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, 310022, People's Republic of China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Cheng
authors.affiliation: Department of Otolaryngology, the Second Affiliated Hospital of School of Medicine, Zhejiang University School of Medicine, Hangzhou, 310058, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Nanjing Medical University, Affiliated Hangzhou Hospital (Hangzhou First People's Hospital), Hangzhou, 310006 People's Republic of China.
authors.forename: Jiaoli
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, 310022, People's Republic of China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Zhong
mesh_terms: D000368:Aged; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C491901:FAS protein, human; D008840:Microfilament Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D019014:fas Receptor; C020324:fascin