Liu Shin-Yun, Shun Chia-Tung, Hung Kuan-Yu, Juan Hsueh-Fen, Hsu Chia-Lang, Huang Min-Chuan, Lai I-Rue
Graduate Institute of Anatomy and Cell Biology College of Medicine, National Taiwan University, Taipei, Taiwan.
Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
Oncotarget. 2016 Mar 8;7(10):11251-62. doi: 10.18632/oncotarget.7081.
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.
糖基化作用影响癌症的恶性程度。在此，我们报告N-乙酰半乳糖胺基转移酶2（GALNT2），一种介导粘蛋白O型糖基化第一步的酶，通过修饰MET（肝细胞生长因子受体）活性来抑制胃腺癌（GCA）的恶性表型。GALNT2的mRNA和蛋白在GCA中表达下调，这种降低与更晚期的疾病阶段和更短的无复发生存期相关。抑制GCA细胞中GALNT2的表达会增加体外细胞生长、迁移和侵袭，以及体内肿瘤转移。GALNT2基因敲低增强了MET的磷酸化，并降低了MET上Tn抗原的表达。用PHA665752抑制MET活性可降低GCA细胞中GALNT2基因敲低所导致的恶性表型。我们的结果表明，GALNT2抑制GCA细胞的恶性潜能，并为O-糖基化在MET活性和GCA进展中的重要性提供了新的见解。
