Oncotarget

Research Papers:

Knockdown of GALNT1 suppresses malignant phenotype of hepatocellular carcinoma by suppressing EGFR signaling

Miao-Juei Huang _, Rey-Heng Hu, Chih-Hsing Chou, Chia-Lang Hsu, Ya-Wen Liu, John Huang, Ji-Shiang Hung, I-Rue Lai, Hsueh-Fen Juan, Sung-Liang Yu, Yao-Ming Wu and Min-Chuan Huang

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Oncotarget. 2015; 6:5650-5665. https://doi.org/10.18632/oncotarget.3117

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Abstract

Miao-Juei Huang1, Rey-Heng Hu2, Chih-Hsing Chou1, Chia-Lang Hsu3, Ya-Wen Liu4, John Huang2, Ji-Shiang Hung2, I-Rue Lai1, Hsueh-Fen Juan3, Sung-Liang Yu5, Yao-Ming Wu2, Min-Chuan Huang1,6

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

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

3Department of Life Science, National Taiwan University, Taipei, Taiwan

4Institute of Molecular Medicine, National Taiwan University College of Medicine, Taipei, Taiwan

5Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan

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

Correspondence to:

Yao-Ming Wu, e-mail: wyaoming@gmail.com

Min-Chuan Huang, e-mail: mchuang@ntu.edu.tw

Keywords: GALNT1, GalNAc-transferase, O-glycosylation, epidermal growth factor receptor, receptor tyrosine kinase

Received: October 09, 2014     Accepted: January 08, 2015     Published: February 04, 2015

ABSTRACT

O-glycosylation is a common protein modification. Aberrant O-glycosylation is associated with many cancers. GALNT1 is a GalNAc-transferase that initiates protein O-glycosylation. We found that GALNT1 is frequently up-regulated in hepatocellular carcinoma (HCC) and is associated with poor patient survival. Overexpression of GALNT1 increased and knockdown decreased HCC cell migration and invasion. Knockdown of GALNT1 inhibited EGF-induced migration and invasion. Knockdown of GALNT1 decreased EGFR activation and increased EGFR degradation, by decreasing EGFR O-glycosylation. This study demonstrates that down-regulation of GALNT1 is sufficient to suppress malignant phenotype of HCC cells by decreasing EGFR signaling. Thus, GALNT1 is a potential target in HCC.


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