Fas-associated factor 1 inhibits tumor growth by suppressing Helicobacter pylori-induced activation of NF-κB signaling in human gastric carcinoma

// Ai-qun Liu 1 , Zhongqiu Xie 2 , Xiao-ni Chen 1 , Jie Feng 1 , Jia-wei Chen 1 , Fu-jun Qin 2 , Lian-ying Ge 1 1 Department of Endoscopy, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi, P.R. China 2 Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA Correspondence to: Ai-qun Liu, email: liuaiqun_2004@hotmail.com Lian-ying Ge, email: gelianying2008@163.com Keywords: gastric cancer, Fas-associated factor 1, NF-κB, Helicobacter pylori Abbreviations: FAF1, Fas-associated factor 1; H. pylori, Helicobacter pylori; IL-8, interleukin-8; NF-κB, nuclear factor-κB; TNF-α, tumor necrosis factor-α Received: September 28, 2016 Accepted: November 08, 2016 Published: December 20, 2016 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.