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肿瘤转移中的谷氨酰胺代谢:基因、机制及治疗靶点

Glutamine metabolism in tumor metastasis: Genes, mechanisms and the therapeutic targets.

作者信息

Zhong Xugang, He Zeju, Yin Li, Fan Yong, Tong Yu, Kang Yao, Bi Qing

机构信息

Department of Orthopedics, Zhejiang Provincial People's Hospital, Hangzhou, China.

Department of Orthopedics, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

出版信息

Heliyon. 2023 Oct 5;9(10):e20656. doi: 10.1016/j.heliyon.2023.e20656. eCollection 2023 Oct.

Abstract

Cancer cells frequently change their metabolism from aerobic glycolysis to lipid metabolism and amino acid metabolism to adapt to the malignant biological behaviours of infinite proliferation and distant metastasis. The significance of metabolic substances and patterns in tumour cell metastasis is becoming increasingly prominent. Tumour metastasis involves a series of significant steps such as the shedding of cancer cells from a primary tumour, resistance to apoptosis, and colonisation of metastatic sites. However, the role of glutamine in these processes remains unclear. This review summarises the key enzymes and transporters involved in glutamine metabolism that are related to the pathogenesis of malignant tumour metastasis. We also list the roles of glutamine in resisting oxidative stress and promoting immune escape. Finally, the significance of targeting glutamine metabolism in inhibiting tumour metastasis was proposed, research in this field improving our understanding of amino acid metabolism rewiring and simultaneously bringing about new and exciting therapeutic prospects.

摘要

癌细胞经常将其代谢从有氧糖酵解转变为脂质代谢和氨基酸代谢,以适应无限增殖和远处转移的恶性生物学行为。代谢物质和模式在肿瘤细胞转移中的意义日益突出。肿瘤转移涉及一系列重要步骤,如癌细胞从原发肿瘤脱落、抗凋亡以及在转移部位定植。然而,谷氨酰胺在这些过程中的作用仍不清楚。本综述总结了参与谷氨酰胺代谢的关键酶和转运体,这些与恶性肿瘤转移的发病机制相关。我们还列出了谷氨酰胺在抵抗氧化应激和促进免疫逃逸中的作用。最后,提出了靶向谷氨酰胺代谢在抑制肿瘤转移中的意义,该领域的研究增进了我们对氨基酸代谢重编程的理解,同时带来了令人兴奋的新治疗前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6608/10565784/dd261d47d99b/gr1.jpg

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