title: ETS2 and Twist1 promote invasiveness of Helicobacter pylori-infected gastric cancer cells by inducing Siah2.
abstract: 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.
authors.affiliation: School of Biological Sciences, National Institute of Science Education and Research (NISER), P.O. Bhimpur-Padanpur, Via Jatni, Dist. Khurda 752050, Odisha, India.
authors.forename: Lopamudra
authors.initials: L
authors.lastname: Das
authors.affiliation: School of Biological Sciences, National Institute of Science Education and Research (NISER), P.O. Bhimpur-Padanpur, Via Jatni, Dist. Khurda 752050, Odisha, India.
authors.forename: Shrikant Babanrao
authors.initials: SB
authors.lastname: Kokate
authors.affiliation: School of Biological Sciences, National Institute of Science Education and Research (NISER), P.O. Bhimpur-Padanpur, Via Jatni, Dist. Khurda 752050, Odisha, India.
authors.forename: Suvasmita
authors.initials: S
authors.lastname: Rath
authors.affiliation: Department of Oncopathology, Acharya Harihar Regional Cancer Centre, Cuttack 753007, Odisha, India.
authors.forename: Niranjan
authors.initials: N
authors.lastname: Rout
authors.affiliation: Department of Gastroenterology, SCB Medical College, Cuttack 753007, Odisha, India.
authors.forename: Shivaram Prasad
authors.initials: SP
authors.lastname: Singh
authors.affiliation: School of Medicine, Division of Gastroenterology, UC San Diego, CA 92093, U.S.A.
authors.forename: Sheila Eileen
authors.initials: SE
authors.lastname: Crowe
authors.affiliation: Division of Bacteriology, National Institute of Cholera and Enteric Diseases (NICED), Kolkata 700010, India.
authors.forename: Asish K
authors.initials: AK
authors.lastname: Mukhopadhyay
authors.affiliation: School of Biological Sciences, National Institute of Science Education and Research (NISER), P.O. Bhimpur-Padanpur, Via Jatni, Dist. Khurda 752050, Odisha, India asima@niser.ac.in.
authors.forename: Asima
authors.initials: A
authors.lastname: Bhattacharyya
mesh_terms: D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D016481:Helicobacter Infections / Q000378:metabolism*; D016480:Helicobacter pylori / Q000472:pathogenicity; D006801:Humans; D066298:In Vitro Techniques; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D050787:Proto-Oncogene Protein c-ets-2 / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D000098563:Seven in Absentia Proteins
chemical_list: C494069:ETS2 protein, human; D009687:Nuclear Proteins; D050787:Proto-Oncogene Protein c-ets-2; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins
keywords: ETS2; H. pylori; Siah2; Twist1; gastric cancer; metastasis