期刊
CANCER LETTERS
卷 450, 期 -, 页码 144-154出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2019.02.039
关键词
Helicobacter pylori; Gastric cancer; RACK1; Integrin beta-1; NF-kappa B
类别
资金
- Graduate Innovation Fund of Jiangxi Province, China [YC2016-B025]
- National Natural Science Foundation of China [81460116, 81470832, 81670507]
- Key Program of Science and Technology Department of Jiangxi Province, China [20171BBG70084]
Receptor of activated protein kinase C 1 (RACK1) is downregulated in gastric cancer and is involved in modulating NF-kappa B signaling pathway activity. However, the underlying molecular mechanisms regulating RACK1 expression are unclear. In this study, we demonstrated that downregulated expression of RACK1 was observed in gastric cancer tissue compared to adjacent normal tissue and was correlated with poor prognosis in patients. Helicobacter pylori (H. pylori) infection downregulated RACK1 expression in concert with canonical NF-kappa B signaling pathway activation in vivo and in vitro. RACK1 overexpression suppressed NF-kappa B signaling pathway activation as well as the release of downstream proinflammatory cytokines. In addition, RACK1 downregulation increased integrin beta-1 expression, while integrin beta-1 silencing decreased NF-kappa B signaling activation. Moreover, H. pylori infection downregulated RACK1 but upregulated integrin beta-1 expression at the precancerous lesion stages in human subjects. Our data indicate that H. pylori infection promotes the upregulation of integrin beta-1 expression via downregulation of RACK1 expression, which subsequently leads to the elevated activation of the NF-kappa B signaling pathway, an essential step in H. pylori-induced carcinogenesis.
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