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

Ai-Qun Liu,Lian-Ying Ge,Xiao-Ni Chen,Jia-Wei Chen,Fu-Jun Qin,Zhongqiu Xie,Jie Feng

doi:10.18632/oncotarget.14033

Ai-Qun Liu, Lian-Ying Ge + Show 5 more

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https://doi.org/10.18632/oncotarget.14033

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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.

Highlights

Gastric cancer is the fourth most common human cancer in the world, with approximately 934,000 new cases and 73,800 deaths occuring every year
We investigated the potential involvement of Fas-associated factor 1 (FAF1) in gastric cancer and asked whether nuclear factor-κB (NF-κB) signaling pathways may mediate this involvement
Consistent with a protective role of FAF1 against gastric cancer, we found that FAF1 overexpression in gastric cancer cell lines reduced their proliferation and increased apoptosis (Figure 2A–2E)

Summary

Introduction

Gastric cancer is the fourth most common human cancer in the world, with approximately 934,000 new cases and 73,800 deaths occuring every year. More than 70% of gastric cancer cases occur in developing countries, with nearly half of all cases occurring in China [1]. Despite rapid advancements in surgery, chemotherapy, and radiation therapies for gastric cancer, 5-year overall survival remains around 29% because of tumor recurrence and distant metastases [2]. We showed that FAF1 mRNA levels are lower in gastric cancer tissue, especially in poorly differentiated tumors, than in healthy gastric tissue [7]. These results suggested that FAF1 plays a role in the progression of gastric carcinogenesis

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