Hyperglycemia and aberrant O-GlcNAcylation: contributions to tumor progression

A number of cancer types have shown an increased prevalence and a higher mortality rate in patients with hyperglycemic associated pathologies. Although the correlation between diabetes and cancer incidence has been increasingly reported, the underlying molecular mechanisms beyond this association ar...

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Published in:Journal of bioenergetics and biomembranes 2018-06, Vol.50 (3), p.175-187
Main Authors: Vasconcelos-dos-Santos, Andréia, de Queiroz, Rafaela Muniz, da Costa Rodrigues, Bruno, Todeschini, Adriane R., Dias, Wagner B.
Format: Article
Language:English
Subjects:
Aberration
Animal Anatomy
Animal Biochemistry
Apoptosis
Biochemistry
Bioorganic Chemistry
Cancer
Cell adhesion & migration
Cell migration
Cell proliferation
Chemistry
Chemistry and Materials Science
Chemotherapy
Deregulation
Diabetes mellitus
Histology
Hyperglycemia
Invasiveness
Metabolism
Mini-Review
Molecular modelling
Morphology
O-GlcNAcylation
Organic Chemistry
Proteins
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Summary:A number of cancer types have shown an increased prevalence and a higher mortality rate in patients with hyperglycemic associated pathologies. Although the correlation between diabetes and cancer incidence has been increasingly reported, the underlying molecular mechanisms beyond this association are not yet fully understood. Recent studies have suggested that high glucose levels support tumor progression through multiple mechanisms that are hallmarks of cancer, including cell proliferation, resistance to apoptosis, increased cell migration and invasiveness, epigenetic regulation (hyperglycemic memory), resistance to chemotherapy and altered metabolism. Most of the above occur because hyperglycemia through hexosamine biosynthetic pathway leads to aberrant O-GlcNAcylation of many intracellular proteins that are involved in those mechanisms. Deregulated O-GlcNAcylation is emerging as a general feature of cancer. Despite strong evidence suggesting that aberrant O-GlcNAcylation is or may be involved in the acquisition of all cancer hallmarks, it remains out of the list of the next generation of emerging hallmarks. Here, we discuss some of the current understanding on how hyperglycemia affects cancer cell biology and how aberrant O-GlcNAcylation stands in this context.
ISSN:0145-479X
1573-6881
DOI:10.1007/s10863-017-9740-x