Knockdown of GALNT1 suppresses malignant phenotype of hepatocellular carcinoma by suppressing EGFR signaling.
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.
Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.
Miao-Juei
MJ
Huang
Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
Rey-Heng
RH
Hu
Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.
Chih-Hsing
CH
Chou
Department of Life Science, National Taiwan University, Taipei, Taiwan.
Chia-Lang
CL
Hsu
Institute of Molecular Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
Ya-Wen
YW
Liu
Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
John
J
Huang
Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
Ji-Shiang
JS
Hung
Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.
I-Rue
IR
Lai
Department of Life Science, National Taiwan University, Taipei, Taiwan.
Hsueh-Fen
HF
Juan
Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
Sung-Liang
SL
Yu
Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
Yao-Ming
YM
Wu
Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.|Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan.
Min-Chuan
MC
Huang
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D015536:Down-Regulation; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques; D006031:Glycosylation; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D017350:N-Acetylgalactosaminyltransferases / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D015398:Signal Transduction; D014162:Transfection; D015854:Up-Regulation; D000097763:Polypeptide N-acetylgalactosaminyltransferase
D066246:ErbB Receptors; D017350:N-Acetylgalactosaminyltransferases; D000097763:Polypeptide N-acetylgalactosaminyltransferase; C512478:EGFR protein, human
GALNT1; GalNAc-transferase; O-glycosylation; epidermal growth factor receptor; receptor tyrosine kinase