ETS2 and Twist1 promote invasiveness of Helicobacter pylori-infected gastric cancer cells by inducing Siah2.
ETS2 and Twist1 promote invasiveness of Helicobacter pylori-infected gastric cancer cells by inducing Siah2.
复制标题
DOI：
10.1042/bcj20160187
复制
发表时间：
2016-06-01
期刊：
影响因子：
--
通讯作者：
Bhattacharyya A
中科院分区：
文献类型：
--
作者：
Das L;Kokate SB;Rath S;Rout N;Singh SP;Crowe SE;Mukhopadhyay AK;Bhattacharyya A
幽门螺杆菌在感染的 GCC 中诱导 ETS2 和 Twist1 表达。 ETS2 和 Twist1 在幽门螺杆菌感染的 GCC 中转录激活 siah2。幽门螺杆菌介导的 Siah2 诱导增强了受感染 GCC 的运动性和侵袭性。幽门螺杆菌感染是导致胃癌发生的最有力因素之一。七缺失同源物 (Siah2) 是一种 E3 泛素连接酶，与多种癌症有关，但其在幽门螺杆菌介导的胃癌发生中的作用尚未确定。我们研究了 Siah2 在胃癌转移中的参与情况，并通过幽门螺杆菌感染的胃上皮癌细胞的侵袭性和迁移性进行评估。培养的胃癌细胞 (GCC) MKN45、AGS 和 Kato III 表现出显着诱导的 Siah2 表达，在受到病原体攻击后侵袭性和迁移性增加。表达 Siah2 的稳定细胞在幽门螺杆菌感染后表现出侵袭性和迁移性增加。 Siah2 被幽门螺杆菌感染的胃上皮细胞中诱导的 E26 转化特异性序列 2 (ETS2) 和 Twist 相关蛋白 1 (Twist1) 转录激活。这些转录因子剂量依赖性地增强了受感染 GCC 的侵袭性。我们的数据表明，幽门螺杆菌感染的 GCC 通过 Siah2 诱导获得了细胞运动性和侵袭性。由于与非癌性胃组织相比，胃癌活检样本也显示出 ETS2、Twist1 和 Siah2 的高度诱导表达，因此我们推测 ETS2 和 Twist1 介导的 Siah2 上调具有潜在的诊断和预后意义，并且可以作为治疗目的。
H. pylori induce ETS2 and Twist1 expression in the infected GCC. ETS2 and Twist1 transcriptionally activate siah2 in the H. pylori-infected GCCs. H. pylori-mediated Siah2 induction enhances motility and invasiveness of the infected GCCs. Helicobacter pylori infection is one of the most potent factors leading to gastric carcinogenesis. The seven in absentia homologue (Siah2) is an E3 ubiquitin ligase which has been implicated in various cancers but its role in H. pylori-mediated gastric carcinogenesis has not been established. We investigated the involvement of Siah2 in gastric cancer metastasis which was assessed by invasiveness and migration of H. pylori-infected gastric epithelial cancer cells. Cultured gastric cancer cells (GCCs) MKN45, AGS and Kato III showed significantly induced expression of Siah2, increased invasiveness and migration after being challenged with the pathogen. Siah2-expressing stable cells showed increased invasiveness and migration after H. pylori infection. Siah2 was transcriptionally activated by E26 transformation-specific sequence 2 (ETS2)- and Twist-related protein 1 (Twist1) induced in H. pylori-infected gastric epithelial cells. These transcription factors dose-dependently enhanced the aggressiveness of infected GCCs. Our data suggested that H. pylori-infected GCCs gained cell motility and invasiveness through Siah2 induction. As gastric cancer biopsy samples also showed highly induced expression of ETS2, Twist1 and Siah2 compared with noncancerous gastric tissue, we surmise that ETS2- and Twist1-mediated Siah2 up-regulation has potential diagnostic and prognostic significance and could be targeted for therapeutic purpose.