Suppression of a sialyltransferase by antisense DNA reduces invasiveness of human colon cancer cells in vitro

Yingting Zhu, Ukorn Srivatana, Asad Ullah, Harish Gagneja, Charles S. Berenson, Peter Lance

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

Transfer of terminal α2,6-linked sialic acids to N-glycans is catalyzed by β-galactoside α2,6-sialyltransferase (ST6Gal I). Expression of ST6Gal I and its products is reportedly increased in colon cancers. To investigate directly the functional effects of ST6Gal I expression, human colon cancer (HT29) cells were transfected with specific antisense DNA. ST6Gal I mRNA and protein were virtually undetectable in six strains of transfected HT29 cells. ST6Gal activity was reduced to 14% of control (P < 0.005) in transfected cells. Expression of terminal α2,6- and α2,3-linked sialic acids, and unmasked N-acetyllactosamine oligosaccharides, respectively, was assessed using flow cytometry and fluoresceinated Sambucus nigra, Maackia amurensis and Erythrina cristagalli lectins. Results indicated a major reduction in expression of α2,6-linked sialic acids and counterbalancing increase in unmasked N-acetyllactosamines in antisense DNA-transfected cells, without altered expression of α2,3-linked sialic acids or ganglioside profiles. The ability of transfected cells to form colonies in soft agar and to invade extracellular matrix material (Matrigel), respectively, in vitro was reduced by approx. 98% (P < 0.0001) and more than 3-fold (P < 0.005) compared to parental HT29 cells. These results indicate that N-glycans bearing terminal α2,6-linked sialic acids may enhance the invasive potential of colon cancer cells.

Original languageEnglish (US)
Pages (from-to)148-160
Number of pages13
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1536
Issue number2-3
DOIs
StatePublished - May 31 2001
Externally publishedYes

Keywords

  • Colorectal neoplasm
  • DNA, antisense
  • Neoplasm invasiveness
  • Sialyltransferase

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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