Helicobacter pylori CagA upregulation of CIP2A is dependent on the Src and MEK/ERK pathways
Helicobacter pylori CagA upregulation of CIP2A is dependent on the Src and MEK/ERK pathways
复制标题
幽门螺杆菌 CagA 对 CIP2A 的上调依赖于 Src 和 MEK/ERK 途径。
DOI：
10.1099/jmm.0.014704-0
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发表时间：
2010-03-01
影响因子：
3
通讯作者：
Jia, Jihui
中科院分区：
文献类型：
--
作者：
Zhao, Dapeng;Liu, Zhifang;Jia, Jihui
幽门螺杆菌被列为I类致癌因素，其在胃中持续定植会诱发胃癌。 PP2A 癌抑制剂 (CIP2A) 是一种新发现的癌蛋白，在胃癌中过度表达。作为一种关键的癌蛋白，CIP2A 还参与胃细胞衰老和增殖的调节。异常的 CIP2A 表达诱导无限的细胞增殖，加上幽门螺杆菌感染引起一些关键蛋白的异常表达，两者相结合，导致胃肿瘤发生。然而，幽门螺杆菌感染与CIP2A表达之间的关系仍不清楚。本研究的目的是验证幽门螺杆菌感染对CIP2A表达水平的影响，并鉴定影响CIP2A表达的幽门螺杆菌信号分子和相应通路。在人胃细胞系中质粒介导的 CagA 表达后，用幽门螺杆菌感染细胞，并通过免疫印迹检查 CIP2A 表达水平。信号抑制剂用于验证涉及哪些信号通路。我们还在 AGS 细胞中进行了 CIP2A 去除和去除后幽门螺杆菌感染。幽门螺杆菌感染诱导的 CIP2A 表达依赖于 cagA 基因表达和 CagA 磷酸化。细菌癌蛋白 CagA 上调 CIP2A 表达，这种上调效应依赖于 Src 和 Ras/丝裂原激活蛋白激酶激酶/细胞外信号调节激酶途径。幽门螺杆菌感染诱导的 Myc 稳定性因 CIP2A 耗竭而部分减弱。我们的研究结果为了解幽门螺杆菌致癌机制提供了进一步的信息。
Helicobacter pylori is classified as a class I carcinogenic factor and its persistent colonization in the stomach induces gastric cancer. Cancerous Inhibitor of PP2A (CIP2A) is a newly identified oncoprotein overexpressed in gastric cancer. Serving as a key oncoprotein, CIP2A also participates in regulation of senescence and proliferation of gastric cells. The combination of aberrant CIP2A expression inducing unlimited cell proliferation, and H. pylori infection eliciting aberrant expression of some key proteins, results in the onset of gastric tumorigenesis. However, the relationship between H. pylori infection and CIP2A expression still remains undefined. The aim of our study was to verify the effect of H. pylori infection on CIP2A expression levels and identify H. pylori signalling molecules and corresponding pathways influencing CIP2A expression. Following plasmid-mediated expression of CagA in human gastric cell lines, the cells were infected with H. pylori and CIP2A expression levels were examined by immunoblotting. Signal inhibitors were used to verify which signal pathways were involved. We also performed CIP2A depletion and H. pylori infection after depletion in AGS cells. H. pylori infection-induced CIP2A expression was dependent on cagA gene expression and CagA phosphorylation. Bacterial oncoprotein CagA upregulated CIP2A expression and this upregulation effect was dependent on Src and Ras/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways. H. pylori infection-induced Myc stabilization was partially attenuated by CIP2A depletion. The results of our study provide further information for understanding the mechanism of H. pylori carcinogenesis.