期刊
CANCER LETTERS
卷 374, 期 2, 页码 292-303出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2016.02.032
关键词
Helicobacter pylori; Wnt/beta-catenin; Nanog; Oct4; Gastric cancer
类别
资金
- National Nature Science Foundation of China [81572460]
Helicobacter pylori (H. pylori) infection is considered a major risk factor for gastric cancer. CagA behaves as a major bacterial oncoprotein playing a key role in H. pylori-induced tumorigenesis. Cancer stem cells (CSCs) are believed to possess the ability to initiate tumorigenesis and promote progression. Although studies have suggested that cancer cells can exhibit CSC-like properties in the tumor microenvironment, it remains unclear whether H. pylori infection could induce the emergence of CSC-like properties in gastric cancer cells and, the underlying mechanism. Here, gastric cancer cells were co-cultured with a CagA-positive H. pylori strain or a CagA isogenic mutant strain. We found that H. pylori-infected gastric cancer cells exhibited CSC-like properties, including an increased expression of CSC specific surface markers CD44 and Lgr5, as well as that of Nanog, Oct4 and c-myc, which are known pluripotency genes, and an increased capacity for self-renewal, whereas these properties were not observed in the CagA isogenic mutant strain-infected cells. Further studies revealed that H. pylori activated Wnt/beta-catenin signaling pathway in a CagA-dependent manner and that the activation of this pathway was dependent upon CagA-positive H. pylori-mediated phosphorylation of beta-catenin at the C-terminal Ser675 and Ser552 residues in a c-met- and/or Akt-dependent manner. We further demonstrated that this activation was responsible for H. pylori-induced CSC-like properties. Moreover, we found the promoter activity of Nanog and Oct4 were upregulated, and beta-catenin was observed to bind to these promoters during H. pylori infection, while a Wnt/beta-catenin inhibitor suppressed promoter activity and binding. Taken together, these results suggest that H. pylori upregulates Nanog and Oct4 via Wnt/beta-catenin signaling pathway to promote CSC-like properties in gastric cancer cells. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据