ETS2 and Twist1 promote invasiveness of Helicobacter pylori-infected gastric cancer cells by inducing Siah2

被引：20
作者：
Das, Lopamudra [1 ]
Kokate, Shrikant Babanrao [1 ]
Rath, Suvasmita [1 ]
Rout, Niranjan [2 ]
Singh, Shivaram Prasad [3 ]
Crowe, Sheila Eileen [4 ]
Mukhopadhyay, Asish K. [5 ]
Bhattacharyya, Asima [1 ]
机构：
[1] NISER, Sch Biol Sci, PO Bhimpur Padanpur,Via Jatni, Jatani 752050, Odisha, India
[2] Acharya Harihar Reg Canc Ctr, Dept Oncopathol, Cuttack 753007, Orissa, India
[3] SCB Med Coll, Dept Gastroenterol, Cuttack 753007, Orissa, India
[4] Univ Calif San Diego, Div Gastroenterol, Sch Med, La Jolla, CA 92093 USA
[5] NICED, Div Bacteriol, Kolkata 700010, India
来源：
BIOCHEMICAL JOURNAL | 2016年 / 473卷
关键词：
ETS2; gastric cancer; H; pylori; metastasis; Siah2; Twist1; APICAL-JUNCTIONAL COMPLEX; DOWN-REGULATION; HOMOLOG; SIGNALING PATHWAYS; BREAST-CANCER; EXPRESSION; APOPTOSIS; PROLIFERATION; METASTASIS; INHIBITION;
D O I：
10.1042/BCJ20160187
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
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页码：1629 / 1640
页数：12
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