巨胞饮介导的肿瘤代谢重编程及靶向治疗策略

桑晓琳; 程海凌; 刘丕旭

doi:10.16689/j.cnki.cn11-9349/r.2026.02.001

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肿瘤代谢与营养电子杂志 ›› 2026, Vol. 13 ›› Issue (2) : 173-179. DOI: 10.16689/j.cnki.cn11-9349/r.2026.02.001

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巨胞饮介导的肿瘤代谢重编程及靶向治疗策略

¹桑晓琳, ²程海凌, ¹刘丕旭

作者信息 +

Macropinocytosis-mediated metabolic reprogramming and therapeutic targeting strategies in cancer

¹Sang Xiaolin, ²Cheng Hailing, ¹Liu Pixu

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文章历史 +

摘要

肿瘤代谢重编程是肿瘤发生与进展的核心特征。巨胞饮作为一种非选择性、高通量的胞吞机制,在肿瘤代谢适应中发挥关键作用。该过程通过细胞膜褶皱形成巨胞饮体,摄取外源性蛋白质、脂质、核酸及坏死细胞碎片,并在溶酶体中降解生成氨基酸、脂肪酸和核苷酸等代谢底物,维持能量代谢和生物合成需求。本文阐述了巨胞饮作用的信号调控网络;系统阐述巨胞饮在氨基酸、脂质和核苷酸代谢中的功能,与线粒体代谢的双向交互,以及在肿瘤侵袭、转移与耐药中的作用;重点讨论靶向巨胞饮的两大治疗策略,阐明其证据强度与临床转化潜能。抑制策略通过阻断巨胞饮切断营养供应并逆转免疫抑制,失控诱导策略通过诱导巨泡式死亡实现非凋亡性肿瘤杀伤。深入理解巨胞饮作用的代谢功能与调控特征,将为肿瘤代谢干预和精准靶向治疗提供重要的临床前研究理论基础。

Abstract

Metabolic reprogramming represents a hallmark of cancer initiation and progression. Accumulating evidence demonstrates that macropinocytosis, a non-selective, high-capacity endocytic pathway, plays a pivotal role in tumor metabolic adaptation. Through membrane ruffling and subsequent macropinosome formation, this process facilitates the internalization of extracellular macromolecules including proteins, lipids, nucleic acids, and necrotic cellular debris. Following lysosomal degradation, these substrates are catabolized into essential metabolic building blocks, including amino acids, fatty acids, and nucleotides, that fuel bioenergetic demands and anabolic processes. This review examines the signaling networks governing macropinocytosis and elucidates its metabolic functions in amino acid, lipid, and nucleotide metabolism. We further describe the bidirectional interplay between macropinocytosis and mitochondrial metabolism, and its contributions to tumor invasion, metastasis, and therapeutic resistance. Two therapeutic strategies targeting macropinocytosis have demonstrated promising efficacy in preclinical studies. Suppression of macropinocytosis deprives tumors of nutrients and alleviates immunosuppression, whereas induction of dysregulated macropinocytosis triggers methuosis-mediated non-apoptotic cell death. Understanding the metabolic dependencies and regulatory circuitries of macropinocytosis will provide foundations for developing metabolism-targeted therapies and precision oncology approaches.

导出引用

桑晓琳, 程海凌, 刘丕旭. 巨胞饮介导的肿瘤代谢重编程及靶向治疗策略[J]. 肿瘤代谢与营养电子杂志. 2026, 13(2): 173-179 https://doi.org/10.16689/j.cnki.cn11-9349/r.2026.02.001

Sang Xiaolin, Cheng Hailing, Liu Pixu. Macropinocytosis-mediated metabolic reprogramming and therapeutic targeting strategies in cancer[J]. Electronic Journal of Metabolism and Nutrition of Cancer. 2026, 13(2): 173-179 https://doi.org/10.16689/j.cnki.cn11-9349/r.2026.02.001

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