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The O-glycosylating enzyme GALNT2 suppresses the malignancy of gastric adenocarcinoma by reducing EGFR activities.


ABSTRACT: Aberrant glycosylation affects the malignant progression of cancers. Here, we report that N-acetyl-galactosaminyltransferase 2 (GALNT2), an enzyme that initiates the mucin type-O glycosylation, suppresses malignant phenotypes in gastric adenocarcinoma (GCA) cells by modifying epidermal growth factor receptor (EGFR) activity. GALNT2 was knocked down using siRNA in AGS and MKN28 cells. The expression of phosphorylated EGFR (pEGFR), phosphorylated Akt (pAkt) and Tn antigen were detected by western blotting. Proliferation, migration and invasion of cells with/without GLANT2-knockdown were assessed. Expression of pEGFR in the resected gastric cancer tissue was analyzed by Immunohistochemical staining, and was correlated with clinicopathological factors. The results showed that GALNT2 knockdown enhanced phosphorylation of EGFR and decreased expression of the Tn antigen on EGFR. Inhibiting EGFR activity with Gefitinib decreased the migration/invasion abilities and reversed the increase pAkt caused by GALNT2 knockdown in GCA cells. The addition of MK2206 (Akt inhibitor) mitigated the migration and invasion abilities of the GALNT2-knockdown cells. Patients with increased expressions of pEGFR in their cancer tissues were associated more metastasis, advanced stage and recurrence after surgical resection. Our results indicate that GALNT2 suppresses the malignant potential of GCA cells through the EGFR-Akt signaling pathway. The significance of O-glycosylation in receptor tyrosine kinases activities and GCA progression deserve further studies.

SUBMITTER: Hu WT 

PROVIDER: S-EPMC6176175 | BioStudies | 2018-01-01T00:00:00Z

REPOSITORIES: biostudies

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