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

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

Research output: Contribution to journal › Article › peer-review

37 Citations (Scopus)

Abstract

Glycosylation 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.

Original language	English
Pages (from-to)	11251-11262
Number of pages	12
Journal	Oncotarget
Volume	7
Issue number	10
DOIs	https://doi.org/10.18632/oncotarget.7081
Publication status	Published - 2016
Externally published	Yes

Keywords

GALNT2
Gastric cancer
Hepatocyte growth factor
O-glycosylation
Receptor tyrosin kinase

ASJC Scopus subject areas

Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.18632/oncotarget.7081

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title = "Mucin glycosylating enzyme GALNT2 suppresses malignancy in gastric adenocarcinoma by reducing MET phosphorylation",

abstract = "Glycosylation 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.",

keywords = "GALNT2, Gastric cancer, Hepatocyte growth factor, O-glycosylation, Receptor tyrosin kinase",

author = "Liu, {Shin Yun} and Shun, {Chia Tung} and Hung, {Kuan Yu} and Juan, {Hsueh Fen} and Hsu, {Chia Lang} and Huang, {Min Chuan} and Lai, {I. Rue}",

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doi = "10.18632/oncotarget.7081",

language = "English",

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T1 - Mucin glycosylating enzyme GALNT2 suppresses malignancy in gastric adenocarcinoma by reducing MET phosphorylation

AU - Liu, Shin Yun

AU - Shun, Chia Tung

AU - Hung, Kuan Yu

AU - Juan, Hsueh Fen

AU - Hsu, Chia Lang

AU - Huang, Min Chuan

AU - Lai, I. Rue

PY - 2016

Y1 - 2016

N2 - Glycosylation 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.

AB - Glycosylation 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.

KW - GALNT2

KW - Gastric cancer

KW - Hepatocyte growth factor

KW - O-glycosylation

KW - Receptor tyrosin kinase

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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