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Helicobacter pylori upregulates Nanog and Oct4 via Wnt/β-catenin signaling pathway to promote cancer stem cell-like properties in human gastric cancer.

Abstract：

: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/β-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 β-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 β-catenin was observed to bind to these promoters during H. pylori infection, while a Wnt/β-catenin inhibitor suppressed promoter activity and binding. Taken together, these results suggest that H. pylori upregulates Nanog and Oct4 via Wnt/β-catenin signaling pathway to promote CSC-like properties in gastric cancer cells.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Yong X,Tang B,Xiao YF,Xie R,Qin Y,Luo G,Hu CJ,Dong H,Yang SM

doi

10.1016/j.canlet.2016.02.032

subject

Has Abstract

pub_date

2016-05-01 00:00:00

pages

292-303

issue

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(16)30100-8

journal_volume

374

pub_type

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Helicobacter pylori upregulates Nanog and Oct4 via Wnt/β-catenin signaling pathway to promote cancer stem cell-like properties in human gastric cancer.