Mordzińska-Rak Aleksandra, Verdeil Grégory, Hamon Yannick, Błaszczak Ewa, Trombik Tomasz
Department of Biochemistry and Molecular Biology, Faculty of Medical Sciences, Medical University of Lublin, 1 Chodzki Street, Lublin, 20-093, Poland.
Department of Oncology UNIL CHUV, University of Lausanne, Lausanne, Switzerland.
Cell Mol Life Sci. 2025 Apr 21;82(1):168. doi: 10.1007/s00018-025-05617-9.
Cholesterol is a unique lipid for all mammalian cells, with important functions in membrane biogenesis and maintenance of proper membrane integrity and fluidity. Therefore, it plays an important role in cellular homeostasis. Dysregulation of cholesterol homeostasis is associated with various diseases in humans, including cardiovascular diseases, inflammatory diseases, neurodegenerative disorders, and cancers. In the tumor microenvironment, intrinsic and extrinsic cellular factors reprogram cholesterol metabolism and consequently promote tumorigenesis. Here, we summarize the current knowledge on molecular mechanisms and functional roles of cholesterol homeostasis and its dysregulation in regard to cancer pathogenesis. We also discuss the interplay of cholesterol metabolism and the ATP-binding cassette (ABC) proteins, highly conserved cellular transmembrane lipid transporters. An emerging role of lipid ABC transporters as potential prognostic tools for cancer progression and invasiveness is emphasized. Targeting both cholesterol metabolism and proteins associated with membrane cholesterol holds promise as a novel therapeutic strategy for cancer treatment.
胆固醇是所有哺乳动物细胞特有的脂质，在膜生物合成以及维持适当的膜完整性和流动性方面具有重要功能。因此，它在细胞稳态中发挥着重要作用。胆固醇稳态失调与人类的各种疾病相关，包括心血管疾病、炎症性疾病、神经退行性疾病和癌症。在肿瘤微环境中，内在和外在的细胞因子会重新编程胆固醇代谢，从而促进肿瘤发生。在这里，我们总结了目前关于胆固醇稳态的分子机制和功能作用及其在癌症发病机制中失调的知识。我们还讨论了胆固醇代谢与ATP结合盒（ABC）蛋白（高度保守的细胞跨膜脂质转运蛋白）之间的相互作用。强调了脂质ABC转运蛋白作为癌症进展和侵袭潜在预后工具的新作用。针对胆固醇代谢和与膜胆固醇相关的蛋白质有望成为一种新的癌症治疗策略。
