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

Journal: Cellular signalling
Published Date: Sep 1, 2025

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.

Authors

  • Tingyu Chen
    National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
  • Yiming Xu
    Department of Computer Science and Technology, Tsinghua University, Beijing, China.
  • Fan Yang
    School of Electrical Engineering and Automation, Jiangsu Normal University, Xuzhou, China.
  • Yanxin Pan
    State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • Ning Ji
    State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • Jing Li
    Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.
  • Xin Zeng
    Electrical and Computer Engineering Department, University of California, Los Angeles, CA, 90095, USA.
  • Qianming Chen
    Department of Oral Medicine, Stomatology Hospital, School of Stomatology & Zhejiang University School of Medicine & Clinical Research Center for Oral Diseases of Zhejiang Province & Key Laboratory of Oral Biomedical Research of Zhejiang Province & Cancer Center of Zhejiang University, Hangzhou 310006, China.
  • Lu Jiang
    Institute of Materials Research and Engineering (IMRE), A*STAR, 2 Fusionopolis Way, #08-03 Innovis, Singapore 138634.
  • Ying-Qiang Shen
    State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address: shen@scu.edu.cn.

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