| Summary: | 博士 === 國立臺灣大學 === 解剖學暨細胞生物學研究所 === 104 === Aberrant glycosylation determines the malignant characters of cancers. 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 the activity of the MET (Hepatocyte growth factor receptor). GALNT2 mRNA and protein were downregulated in GCAs, and these events were associated with more advanced disease and shorter recurrence-free survival. Suppressing GALNT2 expression in GCA cells increased cell growth, migration, and invasion in vitro, and tumor metastasis in vivo. Mechanistic investigations revealed that GALNT2 knockdown enhanced phosphorylation of MET and overexpression of GALNT2 decreased MET phospohrylation. We also revealed that GALNT2 effected the Tn antigen on MET. Inhibiting MET activity with PHA665752 decreased the malignant phenotypes caused by GALNT2 knockdown in GCA cells, establishing the important role of MET in the effects mediated by GALNT2. 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.
Keywords: GALNT2, N-acetylgalactosaminyltransferase, O-glycosylation, Hepatocyte growth factor, Receptor tyrosine kinase, gastric adenocarcinoma (GCA)
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