Crosstalk of glutamine metabolism between cancer-associated fibroblasts and cancer cells

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling Pub Date : 2025-05-15 DOI:10.1016/j.cellsig.2025.111874

Tingyu Chen, Yiming Xu, Fan Yang, Yanxin Pan, Ning Ji, Jing Li, Xin Zeng, Qianming Chen, Lu Jiang, Ying-Qiang Shen

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引用次数: 0

Abstract

Glutamine (Gln), a critical metabolic substrate, fuels the uncontrolled proliferation of cancer cells. Cancer-associated fibroblasts (CAFs), essential components of the tumor microenvironment, facilitate tumor progression by supplying Gln to cancer cells and driving drug resistance through metabolic reprogramming. This review highlights the key processes of Gln uptake, transport, and catabolism and explores the metabolic crosstalk between CAFs and cancer cells. It also examines the roles of major oncogenic regulators—c-Myc, mTORC, KRAS, p53, and HIF—in controlling Gln metabolism and shaping therapeutic resistance. Current pharmacological approaches targeting Gln metabolism, including enzyme inhibitors and transporter blockers, are discussed alongside emerging therapeutic strategies and ongoing clinical trials. Lastly, we underscore the importance of integrating advanced technologies like artificial intelligence and spatial omics to refine treatment targeting and develop more effective, personalized therapeutic interventions.

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肿瘤相关成纤维细胞与癌细胞间谷氨酰胺代谢的串扰

谷氨酰胺（Gln）是一种关键的代谢底物，促进癌细胞不受控制的增殖。癌症相关成纤维细胞（CAFs）是肿瘤微环境的重要组成部分，通过向癌细胞提供谷氨酰胺并通过代谢重编程驱动耐药，从而促进肿瘤进展。本文综述了谷氨酰胺摄取、转运和分解代谢的关键过程，并探讨了谷氨酰胺与癌细胞之间的代谢串扰。它还检查了主要的致癌调节因子- c- myc， mTORC， KRAS， p53和hif在控制Gln代谢和形成治疗抗性中的作用。目前针对谷氨酰胺代谢的药理学方法，包括酶抑制剂和转运蛋白阻滞剂，与新兴的治疗策略和正在进行的临床试验一起讨论。最后，我们强调整合人工智能和空间组学等先进技术的重要性，以完善治疗目标，并开发更有效，个性化的治疗干预措施。

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

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.