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

doi:10.1023/B:GLYC.0000033631.35357.41

Paper

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

Published Jun 1, 2003 · R. Kannagi

Glycoconjugate Journal

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163

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9

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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 ‘neosynthesis.’ 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 ‘neosynthesis,’ recent studies have indicated that cancer-associated alterations in the sugar transportation and intermediate carbohydrate metabolism play important roles. Cancer cells are known to exhibit a metabolic shift from oxidative to elevated anaerobic glycolysis (Warburg effect), which is correlated with the increased gene expression of sugar transporters and glycolytic enzymes induced by common cancer-specific genetic alterations. The increased sialyl Lewis X/A expression in cancer is a link in the chains of these events because our recent results indicated that these events accompany transcriptional induction of a set of genes closely related to its expression. Published in 2004.

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Study Snapshot

Cancer-associated sialyl Lewis X/A expression involves two principal mechanisms: incomplete synthesis and neosynthesis, with epigenetic changes and changes in sugar transport and metabolism playing key roles.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

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

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References

Loss of Disialyl Lewisa, the Ligand for Lymphocyte Inhibitory Receptor Sialic Acid-Binding Immunoglobulin-Like Lectin-7 (Siglec-7) Associated with Increased Sialyl Lewisa Expression on Human Colon Cancers

Disialyl Lewisa expression decreases in colon cancer cells, leading to loss of normal cell-cell recognition and increased sialyl Lewisa expression, potentially contributing to cancer progression.

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Hypoxia-induced metabolic changes in cancer cells enhance their adhesion to vascular endothelial cells, potentially facilitating hematogenous metastasis and tumor angiogenesis.

Carbohydrate‐mediated cell adhesion in cancer metastasis and angiogenesis

Sialyl Lewisa and sialyl Lewisx determinants are functionally implicated in cancer cell behavior and hematogenous metastasis, offering potential therapeutic targets for suppressing hematogenous metastasis.

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ST6GalNAc VI plays a novel substrate specificity role in colon cancer cell lines, synthesizing disialyl Lea from sialyl Lc4, while also competing with FUT-3 for this substrate.

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Tax activates the Fuc-T VII gene promoter in T cells through a variant cAMP-responsive element, similar to the viral CRE in HTLV-1 LTR.

Citations

The Role of Non-Human Sialic Acid Neu5Gc-Containing Glycoconjugates in Human Tumors: A Review of Clinical and Experimental Evidence

Neu5Gc-containing glycoconjugates play a multifaceted role in cancer progression and show potential as prognostic markers and therapeutic targets.

A nomogram prediction model of pseudomyxoma peritonei established based on new prognostic factors of HE stained pathological images analysis

This study developed a new predictive model for pseudomyxoma peritonei using HE-stained pathological images, integrating digital pathological parameters with clinical information.

Precursor carboxy-silica for functionalization with interactive ligands. III. Carbodiimide assisted preparation of immobilized lectin stationary phases for high performance lectin affinity chromatography of sub-glycoproteomics from cancer and disease free human sera.

Precursor carboxy-silica support effectively immobilizes concanavalin A and wheat germ agglutinin for high-performance lectin affinity chromatography, enabling selective capture and enrichment of glycoproteins from healthy and cancer human sera.

Identification of FUT7 hypomethylation as the blood biomarker in prediction of early-stage lung cancer.

FUT7 hypomethylation is a strong blood biomarker for early-stage lung cancer, with potential as a noninvasive diagnostic tool for reducing lung cancer-related mortality.

Preliminary Analysis of the Glycolipid Profile in Secondary Brain Tumors

The study of lipidomics in secondary brain tumors could improve cancer therapy effectiveness by focusing on the specific molecular patterns of these tumors.