法尼醇X受体驱动的代谢可塑性:连接脂质代谢中的生理适应与恶性转化(综述)
Farnesoid X receptor‑driven metabolic plasticity: Bridging physiological adaptation and malignant transformation in lipid handling (Review).
作者信息
Sun Yanning, Sun Kai, Ling Hongju, Xia Qinghua
机构信息
Urology Department, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, P.R. China.
出版信息
Int J Mol Med. 2025 Jul;56(1). doi: 10.3892/ijmm.2025.5551. Epub 2025 May 16.
Metabolic reprogramming represents a hallmark of malignant tumors, manifested through progressive alterations in nutrient utilization patterns during oncogenesis. As fundamental constituents of biological membranes, essential components of signaling pathways, and critical energy substrates, lipids undergo comprehensive metabolic restructuring in neoplastic cells. This lipid remodeling confers enhanced adaptability to sustain uncontrolled proliferation while promoting aggressive migratory phenotypes. Farnesoid X receptor (FXR), a ligand‑activated nuclear receptor responsive to bile acid (BA) derivatives and cholesterol metabolites, orchestrates key aspects of lipid homeostasis. Its regulatory network encompasses cholesterol/BA metabolism, fatty acid (FA) metabolism and plasma lipoprotein trafficking pathways. Emerging evidence positions FXR as a pleiotropic modulator in oncogenesis, with dysregulated expression patterns documented across multiple tumor lineages and premalignant lesions. This mechanistic understanding has propelled FXR‑targeted therapeutics into the forefront of precision oncology development. The present review critically examines the FXR‑lipid axis in lipid‑enriched malignancies, with particular emphasis on its regulatory circuitry governing BA flux and FA turnover.
代谢重编程是恶性肿瘤的一个标志,表现为肿瘤发生过程中营养物质利用模式的渐进性改变。作为生物膜的基本组成成分、信号通路的重要组成部分以及关键的能量底物,脂质在肿瘤细胞中经历全面的代谢重塑。这种脂质重塑赋予肿瘤细胞更强的适应性,以维持不受控制的增殖,同时促进侵袭性迁移表型。法尼酯X受体(FXR)是一种配体激活的核受体,对胆汁酸(BA)衍生物和胆固醇代谢产物有反应,它协调脂质稳态的关键方面。其调控网络包括胆固醇/BA代谢、脂肪酸(FA)代谢和血浆脂蛋白运输途径。越来越多的证据表明FXR在肿瘤发生中是一种多效性调节因子,在多个肿瘤谱系和癌前病变中都有其表达模式失调的记录。这种机制上的认识推动了以FXR为靶点的治疗方法成为精准肿瘤学发展的前沿。本综述批判性地研究了富含脂质的恶性肿瘤中的FXR-脂质轴,特别强调其控制BA通量和FA周转的调控机制。