title: Mucin glycosylating enzyme GALNT2 suppresses malignancy in gastric adenocarcinoma by reducing MET phosphorylation.
abstract: Glycosylation affects malignancy in cancer. Here, we report that N- acetylgalactosaminyltransferase 2 (GALNT2), an enzyme that mediates the initial step of mucin type-O glycosylation, suppresses malignant phenotypes in gastric adenocarcinoma (GCA) by modifying MET (Hepatocyte growth factor receptor) activity. GALNT2 mRNA and protein were downregulated in GCAs, and this reduction was associated with more advanced disease stage and shorter recurrence-free survival. Suppressing GALNT2 expression in GCA cells increased cell growth, migration, and invasion in vitro, and tumor metastasis in vivo. GALNT2 knockdown enhanced phosphorylation of MET and decreased expression of the Tn antigen on MET. Inhibiting MET activity with PHA665752 decreased the malignant phenotypes caused by GALNT2 knockdown in GCA cells. Our results indicate that GALNT2 suppresses the malignant potential of GCA cells and provide novel insights into the significance of O-glycosylation in MET activity and GCA progression.
authors: Graduate Institute of Anatomy and Cell Biology College of Medicine, National Taiwan University, Taipei, Taiwan.
authors: Shin-Yun
authors: SY
authors: Liu
authors: Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
authors: Chia-Tung
authors: CT
authors: Shun
authors: Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Taipei, Taiwan.
authors: Kuan-Yu
authors: KY
authors: Hung
authors: Department of Life Science and Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, Taiwan.
authors: Hsueh-Fen
authors: HF
authors: Juan
authors: Department of Life Science and Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, Taiwan.
authors: Chia-Lang
authors: CL
authors: Hsu
authors: Graduate Institute of Anatomy and Cell Biology College of Medicine, National Taiwan University, Taipei, Taiwan.|Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan.
authors: Min-Chuan
authors: MC
authors: Huang
authors: Graduate Institute of Anatomy and Cell Biology College of Medicine, National Taiwan University, Taipei, Taiwan.|Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors: I-Rue
authors: IR
authors: Lai
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D000368:Aged; D000818:Animals; D005260:Female; D006031:Glycosylation; D064593:Heterografts; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009077:Mucins / Q000378:metabolism; D017350:N-Acetylgalactosaminyltransferases / Q000378:metabolism*; D010766:Phosphorylation; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D009077:Mucins; D017350:N-Acetylgalactosaminyltransferases; D019859:Proto-Oncogene Proteins c-met; D000097763:Polypeptide N-acetylgalactosaminyltransferase; C491743:MET protein, human
keywords: GALNT2; O-glycosylation; gastric cancer; hepatocyte growth factor; receptor tyrosin kinase