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Cells 2018, 7(6), 53; https://doi.org/10.3390/cells7060053

The Nutrient-Sensing Hexosamine Biosynthetic Pathway as the Hub of Cancer Metabolic Rewiring

Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan 20126, Italy
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Received: 30 April 2018 / Revised: 29 May 2018 / Accepted: 31 May 2018 / Published: 2 June 2018
(This article belongs to the Special Issue Mitochondrial Bioenergetics in Cancer Cell Biology)
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Abstract

Alterations in glucose and glutamine utilizing pathways and in fatty acid metabolism are currently considered the most significant and prevalent metabolic changes observed in almost all types of tumors. Glucose, glutamine and fatty acids are the substrates for the hexosamine biosynthetic pathway (HBP). This metabolic pathway generates the “sensing molecule” UDP-N-Acetylglucosamine (UDP-GlcNAc). UDP-GlcNAc is the substrate for the enzymes involved in protein N- and O-glycosylation, two important post-translational modifications (PTMs) identified in several proteins localized in the extracellular space, on the cell membrane and in the cytoplasm, nucleus and mitochondria. Since protein glycosylation controls several key aspects of cell physiology, aberrant protein glycosylation has been associated with different human diseases, including cancer. Here we review recent evidence indicating the tight association between the HBP flux and cell metabolism, with particular emphasis on the post-transcriptional and transcriptional mechanisms regulated by the HBP that may cause the metabolic rewiring observed in cancer. We describe the implications of both protein O- and N-glycosylation in cancer cell metabolism and bioenergetics; focusing our attention on the effect of these PTMs on nutrient transport and on the transcriptional regulation and function of cancer-specific metabolic pathways. View Full-Text
Keywords: hexosamine biosynthesis pathway; UDP-GlcNAc; protein glycosylation; metabolism; bioenergetics; cancer hexosamine biosynthesis pathway; UDP-GlcNAc; protein glycosylation; metabolism; bioenergetics; cancer
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Chiaradonna, F.; Ricciardiello, F.; Palorini, R. The Nutrient-Sensing Hexosamine Biosynthetic Pathway as the Hub of Cancer Metabolic Rewiring. Cells 2018, 7, 53.

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