Liu, S.-Y.S.-Y.LiuCHIA-TUNG SHUNKUAN-YU HUNGJuan, H.-F.H.-F.JuanCHIA-LANG HSUMIN-CHUAN HUANGI-RUE LAI2020-02-272020-02-2720161949-2553https://www.scopus.com/inward/record.uri?eid=2-s2.0-84961988052&doi=10.18632%2foncotarget.7081&partnerID=40&md5=a24e8889f64a4ebe63f9002590bc1111https://scholars.lib.ntu.edu.tw/handle/123456789/465957Glycosylation affects malignancy in cancer. Here, we report that Nacetylgalactosaminyltransferase 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.[SDGs]SDG3messenger RNA; n acetylgalactosaminyltransferase; n acetylgalactosaminyltransferase 2; scatter factor receptor; unclassified drug; MET protein, human; mucin; n acetylgalactosaminyltransferase; polypeptide N-acetylgalactosaminyltransferase; scatter factor receptor; advanced cancer; aged; animal experiment; animal model; animal tissue; Article; cancer growth; cancer staging; cancer survival; cell growth; cell migration; controlled study; disease association; disease free survival; down regulation; female; gene expression profiling; gene expression regulation; human; human cell; human tissue; in vitro study; in vivo study; lymph node metastasis; major clinical study; male; malignant phenotype; malignant potential; molecular dynamics; mouse; nonhuman; oncological parameters; phenotype; protein expression; protein phosphorylation; recurrence free survival; stomach adenocarcinoma; survival rate; survival time; tumor invasion; adenocarcinoma; animal; glycosylation; Kaplan Meier method; metabolism; middle aged; mortality; nude mouse; pathology; phosphorylation; stomach tumor; xenograft; Adenocarcinoma; Aged; Animals; Female; Glycosylation; Heterografts; Humans; Kaplan-Meier Estimate; Male; Mice; Mice, Nude; Middle Aged; Mucins; N-Acetylgalactosaminyltransferases; Phosphorylation; Proto-Oncogene Proteins c-met; Stomach Neoplasmsjournal article10.18632/oncotarget.7081268489762-s2.0-84961988052