Helicobacter pylori FKBP-type PPIase promotes gastric epithelial cell proliferation and anchorage-independent growth through activation of ERK-mediated mitogenic signaling pathway | Zendy

Yanmei Zhu | Zendy; Moye Chen | Zendy; Yuehua Gong | Zendy; Ziyang Liu | Zendy; Aodi Li | Zendy; Dan Kang | Zendy; Fang Han | Zendy; Jingwei Liu | Zendy; Jun Liu | Zendy; Yuan Yuan | Zendy

Open Access

Helicobacter pylori FKBP-type PPIase promotes gastric epithelial cell proliferation and anchorage-independent growth through activation of ERK-mediated mitogenic signaling pathway

Author(s) -

Yanmei Zhu,

Moye Chen,

Yuehua Gong,

Ziyang Liu,

Aodi Li,

Dan Kang,

Fang Han,

Jingwei Liu,

Jun Liu,

Yuan Yuan

Publication year - 2015

Publication title -

fems microbiology letters

Language(s) - English

Resource type - Journals

eISSN - 1574-6968

pISSN - 0378-1097

DOI - 10.1093/femsle/fnv023

Subject(s) - helicobacter pylori , signal transduction , cell growth , biology , mapk/erk pathway , ectopic expression , phosphorylation , caga , microbiology and biotechnology , peptidylprolyl isomerase , cancer research , cell culture , isomerase , biochemistry , virulence , genetics , gene

Though Helicobacter pylori (H. pylori) has been classified as class I carcinogen, key virulence factor(s) generated by H. pylori that causes gastric cancer remains to be fully determined. Here, we show that deletion of peptidyl-prolyl cis-trans isomerase (PPIase) prevented H. pylori from stimulating human gastric epithelial cell (AGS) proliferation. Consistent with this observation, ectopic expression of H. pylori PPIase promoted AGS cell proliferation and anchorage-independent growth. To gain insight into the biochemical mechanism of PPIase-induced effect, early signal events involved in mitogenic signaling pathways were evaluated. Expression of H. pylori PPIase caused an increase in basal as well as EGF-stimulated phosphorylation of ERK and EGF receptor at Tyr1086. Treatment with MEK inhibitor completely blocked PPIase-induced cell proliferation. Our results suggest that H. pylori PPIase has the potential to activate mitogenic signaling pathway and to promote transformation of gastric epithelial cells. H. pylori PPIase may represent a novel target for therapeutic management of gastric cancer patients.

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