Knockdown of GALNT1 suppresses malignant phenotype of hepatocellular carcinoma by suppressing EGFR signaling
Journal
Oncotarget
Journal Volume
6
Journal Issue
8
Pages
5650
Date Issued
2015
Author(s)
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.
SDGs
Other Subjects
early endosome antigen 1; epidermal growth factor receptor; lysosome associated membrane protein 1; messenger RNA; n acetylgalactosaminyltransferase; n acetylgalactosaminyltransferase 1; unclassified drug; EGFR protein, human; epidermal growth factor receptor; n acetylgalactosaminyltransferase; polypeptide N-acetylgalactosaminyltransferase; animal experiment; animal model; animal tissue; Article; cell invasion; cell migration; cellular distribution; controlled study; female; gene expression; human; human cell; human tissue; liver cancer cell line; liver cell carcinoma; mouse; nonhuman; overall survival; protein degradation; protein glycosylation; signal transduction; upregulation; animal; antagonists and inhibitors; cell proliferation; deficiency; down regulation; gene silencing; genetic transfection; genetics; glycosylation; Hep-G2 cell line; liver cell carcinoma; liver tumor; metabolism; nonobese diabetic mouse; pathology; phenotype; physiology; SCID mouse; tumor cell line; Animals; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; Down-Regulation; Female; Gene Knockdown Techniques; Glycosylation; Hep G2 Cells; Humans; Liver Neoplasms; Mice; Mice, Inbred NOD; Mice, SCID; N-Acetylgalactosaminyltransferases; Phenotype; Receptor, Epidermal Growth Factor; Signal Transduction; Transfection; Up-Regulation
Publisher
Impact Journals LLC
Type
journal article