title: Fas-associated factor 1 inhibits tumor growth by suppressing Helicobacter pylori-induced activation of NF-κB signaling in human gastric carcinoma.
abstract: Loss of Fas-associated factor 1 (FAF1) may act as a pro-survival signal in diseased cells, but whether this is true in gastric carcinoma remains unclear. Here we report that FAF1 was expressed at low levels in gastric carcinoma tissues and cell lines, and its expression correlated with larger tumors, higher histology grade, higher TNM stage, tumor infiltration, and lymph node metastasis. Univariate analysis and survival curve analysis identified low FAF1 expression as a predictor of poor prognosis. FAF1 overexpression in HGC-27 gastric cancer cells induced cell apoptosis and inhibited cell proliferation and growth. It also reduced colony formation in vitro and tumor growth in mice. We found that Helicobacter pylori, a risk factor for gastric cancer, down-regulated FAF1 expression via NF-κB signaling. Knock-down of IKKβ or p65 expression in gastric cancer cells reversed H. pylori-induced down-regulation of FAF1 expression and partially blocked H. pylori-induced secretion of inflammatory cytokines TNF-α and IL-8. Our results suggest that loss of FAF1 contributes to human gastric carcinogenesis by allowing H. pylori to activate NF-κB signaling.
authors.affiliation: Department of Endoscopy, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi, P.R. China.
authors.forename: Ai-Qun
authors.initials: AQ
authors.lastname: Liu
authors.affiliation: Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Department of Endoscopy, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi, P.R. China.
authors.forename: Xiao-Ni
authors.initials: XN
authors.lastname: Chen
authors.affiliation: Department of Endoscopy, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Endoscopy, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi, P.R. China.
authors.forename: Jia-Wei
authors.initials: JW
authors.lastname: Chen
authors.affiliation: Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Fu-Jun
authors.initials: FJ
authors.lastname: Qin
authors.affiliation: Department of Endoscopy, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi, P.R. China.
authors.forename: Lian-Ying
authors.initials: LY
authors.lastname: Ge
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D016481:Helicobacter Infections / Q000382:microbiology*; D016480:Helicobacter pylori / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D060066:Protein Interaction Maps; D034622:RNA Interference; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D013997:Time Factors; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D047368:Tumor Burden; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C508606:CXCL8 protein, human; C490780:FAF1 protein, human; D016209:Interleukin-8; D016328:NF-kappa B; C498143:RELA protein, human; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D051550:I-kappa B Kinase; C496560:IKBKB protein, human
keywords: Fas-associated factor 1; Helicobacter pylori; NF-κB; gastric cancer