Suppression of cancer progression by MGAT1 shRNA knockdown

PLoS One. 2012;7(9):e43721. doi: 10.1371/journal.pone.0043721. Epub 2012 Sep 5.


Oncogenic signaling promotes tumor invasion and metastasis, in part, by increasing the expression of tri- and tetra- branched N-glycans. The branched N-glycans bind to galectins forming a multivalent lattice that enhances cell surface residency of growth factor receptors, and focal adhesion turnover. N-acetylglucosaminyltransferase I (MGAT1), the first branching enzyme in the pathway, is required for the addition of all subsequent branches. Here we have introduced MGAT1 shRNA into human HeLa cervical and PC-3-Yellow prostate tumor cells lines, generating cell lines with reduced transcript, enzyme activity and branched N-glycans at the cell surface. MGAT1 knockdown inhibited HeLa cell migration and invasion, but did not alter cell proliferation rates. Swainsonine, an inhibitor of α-mannosidase II immediately downstream of MGAT1, also inhibited cell invasion and was not additive with MGAT1 shRNA, consistent with a common mechanism of action. Focal adhesion and microfilament organization in MGAT1 knockdown cells also indicate a less motile phenotype. In vivo, MGAT1 knockdown in the PC-3-Yellow orthotopic prostate cancer xenograft model significantly decreased primary tumor growth and the incidence of lung metastases. Our results demonstrate that blocking MGAT1 is a potential target for anti-cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Disease Progression
  • Enzyme Inhibitors / pharmacology
  • Female
  • HeLa Cells
  • Humans
  • Male
  • Mice
  • N-Acetylglucosaminyltransferases / genetics*
  • N-Acetylglucosaminyltransferases / metabolism
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Neoplasms / genetics*
  • Neoplasms / therapy*
  • Phenotype
  • Polysaccharides / chemistry
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / therapy
  • RNA, Small Interfering / metabolism*
  • Signal Transduction
  • Swainsonine / pharmacology


  • Enzyme Inhibitors
  • Polysaccharides
  • RNA, Small Interfering
  • MGAT1 protein, human
  • N-Acetylglucosaminyltransferases
  • Swainsonine