Molecular mechanism for cancer-associated induction of sialyl Lewis X and sialyl Lewis A expression-The Warburg effect revisited

Glycoconjugate Journal
R Kannagi

Abstract

Cell adhesion mediated by selectins and their carbohydrate ligands, sialyl Lewis X and sialyl Lewis A, figures heavily in cancer metastasis. Expression of these carbohydrate determinants is markedly enhanced in cancer cells, but the molecular mechanism that leads to cancer-associated expression of sialyl Lewis X/A has not been well understood. Results of recent studies indicated involvement of two principal mechanisms in the accelerated expression of sialyl Lewis X/A in cancers; 'incomplete synthesis' and ' neo synthesis.' As to 'incomplete synthesis,' we have recently found further modified forms of sialyl Lewis X and sialyl Lewis A in non-malignant colonic epithelium, which have additional 6-sulfation or 2 --> 6 sialylation. The impairment of GlcNAc 6-sulfation and 2 --> 6 sialylation upon malignant transformation leads to accumulation of sialyl Lewis X/A in colon cancer cells. Epigenetic changes such as DNA methylation and/or histone deacetylation are suggested to lie behind such incomplete synthesis. As to the mechanism called ' neo synthesis,' recent studies have indicated that cancer-associated alterations in the sugar transportation and intermediate carbohydrate metabolism play important roles. Cancer cells are known to ...Continue Reading

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