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Review
. 2023 Jan;1867(1):130250.
doi: 10.1016/j.bbagen.2022.130250. Epub 2022 Oct 10.

Dysregulation of hexosamine biosynthetic pathway wiring metabolic signaling circuits in cancer

Naoki Itano  1 , Shungo Iwamoto  2
Affiliations
Review

Dysregulation of hexosamine biosynthetic pathway wiring metabolic signaling circuits in cancer

Naoki Itano et al. Biochim Biophys Acta Gen Subj. 2023 Jan.

Abstract

Metabolite sensing, a fundamental biological process, plays a key role in metabolic signaling circuit rewiring. Hexosamine biosynthetic pathway (HBP) is a glucose metabolic pathway essential for the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), which senses key nutrients and integrally maintains cellular homeostasis. UDP-GlcNAc dynamically regulates protein N-glycosylation and O-linked-N-acetylglucosamine modification (O-GlcNAcylation). Dysregulated HBP flux leads to abnormal protein glycosylation, and contributes to cancer development and progression by affecting protein function and cellular signaling. Furthermore, O-GlcNAcylation regulates cellular signaling pathways, and its alteration is linked to various cancer characteristics. Additionally, recent findings have suggested a close association between HBP stimulation and cancer stemness; an elevated HBP flux promotes cancer cell conversion to cancer stem cells and enhances chemotherapy resistance via downstream signal activation. In this review, we highlight the prominent roles of HBP in metabolic signaling and summarize the recent advances in HBP and its downstream signaling, relevant to cancer.

Keywords: Cancer stem cells; Hexosamine biosynthetic pathway; Metabolic signaling; N-glycosylation; O-GlcNAcylation.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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