CagA Associates with c-Met, E-Cadherin, and p120-Catenin in a Multiproteic Complex That Suppresses Helicobacter pylori-Induced Cell-Invasive Phenotype
CagA Associates with c-Met, E-Cadherin, and p120-Catenin in a Multiproteic Complex That Suppresses Helicobacter pylori-Induced Cell-Invasive Phenotype
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DOI：
10.1086/604727
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发表时间：
2009-09-01
影响因子：
6.4
通讯作者：
Figueiredo, Ceu
中科院分区：
文献类型：
--
作者：
Oliveira, Maria Jose;Costa, Angela Margarida;Figueiredo, Ceu
背景幽门螺杆菌通过需要IV型分泌系统和c-Met磷酸化的机制诱导胃上皮细胞的侵袭表型。E-钙粘蛋白-连环蛋白复合物是粘附连接的主要成分，并作为侵袭抑制因子发挥作用。我们研究了E-cadherin是否在H。pylori诱导的c-Met磷酸化依赖的细胞侵袭表型。AGS细胞缺乏E-cadherin，对H. pylori刺激后，用E-钙粘蛋白转导并感染H.幽门。NCI-N87细胞，其内源性表达E-cadherin，也用于感染实验。E-cadherin不仅能抑制H. pylori介导的细胞侵袭表型，以及c-Met和p120-catenin酪氨酸磷酸化。H. pylori感染导致E-cadherin和p120-catenin、c-Met和E-cadherin以及c-Met和p120-catenin之间的相互作用增加。利用体外感染试验，我们发现H。pylori CagA与E-钙粘蛋白、p120-连环蛋白和c-Met相互作用。最后，利用小分子干扰RNA，我们发现CagA和E-cadherin之间以及CagA和p120-catenin之间的相互作用是通过c-Met建立的。我们建议H.幽门螺杆菌改变了E-钙粘蛋白-连环蛋白复合物，导致由CagA、c-Met、E-钙粘蛋白和p120-连环蛋白组成的多蛋白复合物的形成。该复合物消除c-Met和p120-catenin酪氨酸磷酸化，并抑制H.幽门。
Background. Helicobacter pylori induces an invasive phenotype in gastric epithelial cells through a mechanism that requires the type IV secretion system and the phosphorylation of c-Met. The E-cadherin-catenin complex is a major component of the adherens junctions and functions as an invasion suppressor. We investigated whether E-cadherin has a role in H. pylori-induced, c-Met phosphorylation- dependent cell-invasive phenotype.Methods. AGS cells that lack E-cadherin and that are invasive to H. pylori stimulation were transduced with E-cadherin and infected with H. pylori. NCI-N87 cells, which endogenously express E-cadherin, were also used for infection experiments.Results. E-cadherin was sufficient to suppress not only H. pylori-mediated cell-invasive phenotype but also c-Met and p120-catenin tyrosine phosphorylation. H. pylori infection led to increased interactions between E-cadherin and p120-catenin, c-Met and E-cadherin, and c-Met and p120-catenin. Using in vitro infection assays, we showed that H. pylori CagA interacts with E-cadherin, p120-catenin, and c-Met. Finally, using small interfering RNA, we showed that interactions between CagA and E-cadherin and between CagA and p120-catenin were established through c-Met.Conclusions. We suggest that H. pylori alters the E-cadherin-catenin complex, leading to formation of a multiproteic complex composed of CagA, c-Met, E-cadherin, and p120-catenin. This complex abrogates c-Met and p120-catenin tyrosine phosphorylation and suppresses the cell-invasive phenotype induced by H. pylori.