Knockdown of α2,3-Sialyltransferases Impairs Pancreatic Cancer Cell Migration, Invasion and E-selectin-Dependent Adhesion

Int J Mol Sci. 2020 Aug 28;21(17):6239. doi: 10.3390/ijms21176239.


Aberrant sialylation is frequently found in pancreatic ductal adenocarcinoma (PDA). α2,3-Sialyltransferases (α2,3-STs) ST3GAL3 and ST3GAL4 are overexpressed in PDA tissues and are responsible for increased biosynthesis of sialyl-Lewis (sLe) antigens, which play an important role in metastasis. This study addresses the effect of α2,3-STs knockdown on the migratory and invasive phenotype of PDA cells, and on E-selectin-dependent adhesion. Characterization of the cell sialome, the α2,3-STs and fucosyltransferases involved in the biosynthesis of sLe antigens, using a panel of human PDA cells showed differences in the levels of sialylated determinants and α2,3-STs expression, reflecting their phenotypic heterogeneity. Knockdown of ST3GAL3 and ST3GAL4 in BxPC-3 and Capan-1 cells, which expressed moderate to high levels of sLe antigens and α2,3-STs, led to a significant reduction in sLex and in most cases in sLea, with slight increases in the α2,6-sialic acid content. Moreover, ST3GAL3 and ST3GAL4 downregulation resulted in a significant decrease in cell migration and invasion. Binding and rolling to E-selectin, which represent key steps in metastasis, were also markedly impaired in the α2,3-STs knockdown cells. Our results indicate that inhibition of ST3GAL3 and ST3GAL4 may be a novel strategy to block PDA metastasis, which is one of the reasons for its dismal prognosis.

Keywords: E-selectin; cell migration; pancreatic ductal adenocarcinoma; sialyl-Lewis antigens; α2,3-sialyltransferases.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • E-Selectin / metabolism*
  • Fucosyltransferases / genetics
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Lewis Blood Group Antigens / metabolism
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • RNA, Small Interfering / pharmacology*
  • Sialyltransferases / antagonists & inhibitors
  • Sialyltransferases / genetics*


  • E-Selectin
  • Lewis Blood Group Antigens
  • RNA, Small Interfering
  • SELE protein, human
  • Fucosyltransferases
  • ST3GAL3 protein, human
  • Sialyltransferases
  • ST3GAL4 protein, human