Mucin glycosylating enzyme GALNT2 suppresses malignancy in gastric adenocarcinoma by reducing MET phosphorylation

Shin-Yun Liu; Chia-Tung Shun; Kuan-Yu Hung; Hsueh-Fen Juan; Chia-Lang Hsu; Min-Chuan Huang; I-Rue Lai

doi:10.18632/oncotarget.7081

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Research Papers:

Mucin glycosylating enzyme GALNT2 suppresses malignancy in gastric adenocarcinoma by reducing MET phosphorylation

Shin-Yun Liu, Chia-Tung Shun, Kuan-Yu Hung, Hsueh-Fen Juan, Chia-Lang Hsu, Min-Chuan Huang and I-Rue Lai _

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Oncotarget. 2016; 7:11251-11262. https://doi.org/10.18632/oncotarget.7081

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Abstract

Shin-Yun Liu1, Chia-Tung Shun2, Kuan-Yu Hung3, Hsueh-Fen Juan5, Chia-Lang Hsu5, Min-Chuan Huang1,6, I-Rue Lai1,4

1Graduate Institute of Anatomy and Cell Biology College of Medicine, National Taiwan University, Taipei, Taiwan

2Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan

3Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Taipei, Taiwan

4Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan

5Department of Life Science and Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, Taiwan

6Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan

Correspondence to:

Min-Chuan Huang, e-mail: [email protected]

I-Rue Lai, e-mail: [email protected]

Keywords: gastric cancer, GALNT2, O-glycosylation, hepatocyte growth factor, receptor tyrosin kinase

Received: August 06, 2015 Accepted: January 17, 2016 Published: January 30, 2016

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.

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Research Papers:

Mucin glycosylating enzyme GALNT2 suppresses malignancy in gastric adenocarcinoma by reducing MET phosphorylation

Abstract