Hypersialylation of β 1 integrins, observed in colon adenocarcinoma, may contribute to cancer progression by up-regulating cell motility

Academic Article

Abstract

  • Colon adenocarcinomas are known to express elevated levels of α2-6 sialylation and increased activity of ST6Gal-I, the Golgi glycosyltransferase that creates α2-6 linkages. Elevated ST6Gal-I positively correlates with metastasis and poor survival, and therefore ST6Gal-I-mediated hypersialylation likely plays a role in colorectal tumor invasion. Previously we found that oncogenic ras (present in roughly 50% of colon adenocarcinomas) up-regulates ST6Gal-I and, in turn, increases sialylation of β 1 integrin adhesion receptors in colon epithelial cells. However, we wanted to know if this pattern held true in vivo and, if so, how β 1 hypersialylation might contribute to colon tumor progression. In the present study, we find that β 1 integrins from colon adenocarcinomas consistently carry higher levels of α2-6 sialic acid. To explore the effects of increased α2-6 sialylation on β 1-integrin function, we stably expressed ST6Gal-I in a colon epithelial cell line lacking endogenous ST6Gal-I. ST6Gal-I expressors (with α2-6 sialylated β 1 integrins) exhibited up-regulated attachment to collagen I and laminin and increased haptotactic migration toward collagen I, relative to parental cells (with completely unsialylated β 1 integrins). Blockade of ST6Gal-I expression with short interfering RNA reversed collagen binding back to the level of ST6Gal-I nonexpressors, confirming that α2-6 sialylation regulates β 1 integrin function. Finally, we show that β 1 integrins from ST6Gal-I expressors have increased association with talin, a marker for integrin activation. Collectively, these findings suggest that β 1 hypersialylation may augment colon tumor progression by altering cell preference for certain extracellular matrix milieus, as well as by stimulating cell migration. ©2005 American Association for Cancer Research.
  • Digital Object Identifier (doi)

    Author List

  • Seales EC; Jurado GA; Brunson BA; Wakefield JK; Frost AR; Bellis SL
  • Start Page

  • 4645
  • End Page

  • 4652
  • Volume

  • 65
  • Issue

  • 11