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

// Miao-Juei Huang 1 , Rey-Heng Hu 2 , Chih-Hsing Chou 1 , Chia-Lang Hsu 3 , Ya-Wen Liu 4 , John Huang 2 , Ji-Shiang Hung 2 , I-Rue Lai 1 , Hsueh-Fen Juan 3 , Sung-Liang Yu 5 , Yao-Ming Wu 2 , Min-Chuan Huang 1, 6 1 Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan 2 Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan 3 Department of Life Science, National Taiwan University, Taipei, Taiwan 4 Institute of Molecular Medicine, National Taiwan University College of Medicine, Taipei, Taiwan 5 Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan 6 Research 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.