Exploring the metabolic signaling network of GFPT in cancer.

IF 7 2区生物学 Q1 CELL BIOLOGY

Cell Death Discovery Pub Date : 2025-08-19 DOI:10.1038/s41420-025-02687-3

Chibuzo Sampson, Pengfei Li, Yiqian Wang, Jing Liu, Jing Lv, Tian Xia, Hai-Long Piao, Yegang Ma

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Abstract

Metabolic homeostasis is essential for cellular function in living organisms. In cancer cells, metabolic processes are reprogrammed to meet the energy demands and biosynthetic needs for rapid growth. This reprogramming enhances nutrient flux through the glycolytic pathway, supporting ATP production and branching into pathways that synthesize macromolecules required for cell proliferation. One critical branching pathway is the hexosamine biosynthesis pathway (HBP), which, driven by metabolic reprogramming, facilitates the synthesis of uridine-5'-diphospho-N-acetylglucosamine (UDP-GlcNAc), a glycosylation substrate. This pathway is regulated by the rate-limiting enzyme glutamine-fructose-6-phosphate transaminase (GFPT), a key controller of cellular UDP-GlcNAc levels and protein glycosylation. Dysregulation of GFPT is linked to metabolic disorders, like in diabetes, and it is also frequently upregulated in cancers. Given that GFPT plays a pivotal role in cancer metabolism, elucidating its regulatory interactions with other metabolic signaling pathways under metabolic stress is crucial to identifying therapeutic vulnerabilities in cancer. This review discusses the interaction network of GFPT with other metabolic pathways, its role in nutrient sensing, and the implications of GFPT deregulation in cancer.

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探讨GFPT在癌症中的代谢信号网络。

代谢稳态对生物体的细胞功能至关重要。在癌细胞中，代谢过程被重新编程以满足快速生长的能量需求和生物合成需求。这种重编程增强了糖酵解途径的营养通量，支持ATP的产生，并分支成合成细胞增殖所需大分子的途径。一个关键的分支途径是己糖胺生物合成途径（HBP），它在代谢重编程的驱动下，促进糖基化底物尿苷-5'-二磷酸- n -乙酰氨基葡萄糖胺（UDP-GlcNAc）的合成。该途径受谷氨酰胺-果糖-6-磷酸转氨酶（GFPT）调控，GFPT是细胞内UDP-GlcNAc水平和蛋白糖基化的关键控制者。GFPT的失调与代谢紊乱有关，比如糖尿病，它也经常在癌症中上调。鉴于GFPT在癌症代谢中起着关键作用，阐明其在代谢应激下与其他代谢信号通路的调节相互作用对于确定癌症治疗脆弱性至关重要。这篇综述讨论了GFPT与其他代谢途径的相互作用网络，它在营养感知中的作用，以及GFPT在癌症中失调的意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

8.30

自引率

1.40%

发文量

468

审稿时长

9 weeks

期刊介绍： Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.