title: Helicobacter pylori CagA promotes Snail-mediated epithelial-mesenchymal transition by reducing GSK-3 activity.
abstract: Cytotoxin-associated gene A (CagA) is an oncoprotein and a major virulence factor of H. pylori. CagA is delivered into gastric epithelial cells via a type IV secretion system and causes cellular transformation. The loss of epithelial adhesion that accompanies the epithelial-mesenchymal transition (EMT) is a hallmark of gastric cancer. Although CagA is a causal factor in gastric cancer, the link between CagA and the associated EMT has not been elucidated. Here, we show that CagA induces the EMT by stabilizing Snail, a transcriptional repressor of E-cadherin expression. Mechanistically we show that CagA binds GSK-3 in a manner similar to Axin and causes it to shift to an insoluble fraction, resulting in reduced GSK-3 activity. We also find that the level of Snail protein is increased in H. pylori infected epithelium in clinical samples. These results suggest that H. pylori CagA acts as a pathogenic scaffold protein that induces a Snail-mediated EMT via the depletion of GSK-3.
authors: 1] Department of Internal Medicine and Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea [2].
authors: Da-Gyum
authors: DG
authors: Lee
authors: 1] Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul 120-752, Korea [2].
authors: Hyun Sil
authors: HS
authors: Kim
authors: Department of Internal Medicine and Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors: Yeo Song
authors: YS
authors: Lee
authors: Department of Internal Medicine and Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors: Shin
authors: S
authors: Kim
authors: Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul 120-752, Korea.
authors: So Young
authors: SY
authors: Cha
authors: Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, Kashihara, Nara 634-8522, Japan.
authors: Ichiro
authors: I
authors: Ota
authors: Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul 120-752, Korea.
authors: Nam Hee
authors: NH
authors: Kim
authors: Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul 120-752, Korea.
authors: Yong Hoon
authors: YH
authors: Cha
authors: Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul 120-752, Korea.
authors: Dong Hyun
authors: DH
authors: Yang
authors: Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul 120-752, Korea.
authors: Yoonmi
authors: Y
authors: Lee
authors: Department of Oral Histology, The School of Dentistry, Dankook University, Cheonan-si, Chungnam 330-714, Korea.
authors: Gyeong-Ju
authors: GJ
authors: Park
authors: Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul 120-752, Korea.
authors: Jong In
authors: JI
authors: Yook
authors: Department of Internal Medicine and Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors: Yong Chan
authors: YC
authors: Lee
mesh_terms: D000942:Antigens, Bacterial / Q000502:physiology*; D001426:Bacterial Proteins / Q000502:physiology*; D001706:Biopsy; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005753:Gastric Mucosa / Q000378:metabolism; D005756:Gastritis / Q000378:metabolism / Q000473:pathology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D015398:Signal Transduction / Q000502:physiology; D000071250:Snail Family Transcription Factors; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C080866:cagA protein, Helicobacter pylori; D038362:Glycogen Synthase Kinase 3