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

Oncotarget. 2015 Mar 20;6(8):5650-65. doi: 10.18632/oncotarget.3117.


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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Down-Regulation
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Female
  • Gene Knockdown Techniques
  • Glycosylation
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • N-Acetylgalactosaminyltransferases / deficiency*
  • N-Acetylgalactosaminyltransferases / genetics*
  • N-Acetylgalactosaminyltransferases / metabolism
  • Phenotype
  • Polypeptide N-acetylgalactosaminyltransferase
  • Signal Transduction
  • Transfection
  • Up-Regulation


  • N-Acetylgalactosaminyltransferases
  • EGFR protein, human
  • ErbB Receptors