J Exp Med:脂质代谢与肿瘤发生发展的相互关系

2020-12-31 Bio生物世界 Bio生物世界

该论文全面总结了肿瘤细胞脂质代谢调节的研究进展,并介绍了已被临床用于干扰脂质代谢的肿瘤治疗新方法,同时基于现有研究成果对该领域的未来发展趋势作了深入的讨论与分析。

肿瘤已成为威胁人类健康的首要杀手,对于肿瘤代谢的研究将为肿瘤治疗提供新的靶点。

2020年12月19日,浙江大学转化医学研究院吕志民教授团队 (吕志民教授曾是美国德州大学M.D.安德森癌症中心杰出终身讲席教授和研究成就奖的获得者) 在 Journal of Experimental Medicine 杂志上发表了题为:Lipid metabolism and cancer 的长篇综述论文。

该论文全面总结了肿瘤细胞脂质代谢调节的研究进展,并介绍了已被临床用于干扰脂质代谢的肿瘤治疗新方法,同时基于现有研究成果对该领域的未来发展趋势作了深入的讨论与分析。

脂质以及蛋白质和核酸是构成细胞的生物膜和结构单元的重要组成部分。此外,脂质还用于能量存储和代谢,并在多种细胞活动中起着重要的信号分子作用。脂质代谢的调控,如脂质摄取,合成和水解,对于维持细胞稳态必不可少。在肿瘤进展过程中,肿瘤微环境中营养物质的可用性不断变化,因而肿瘤细胞利用脂质代谢来维持其快速增殖,存活,迁移,侵袭和转移。

作为代谢研究领域的领军学者之一,吕志民教授对肿瘤细胞能量代谢的研究取得了开创性、系统性的重要成果。吕志民团队于2020年初发表在Nature上的工作(详见BioArt报道:Nature | 吕志民/洪明奇合作揭示肿瘤细胞特异性脂质合成代谢机制),揭示了肿瘤细胞特异性脂质合成代谢机制,首次发现了糖异生代谢酶PCK1具有蛋白激酶活性,揭示了PCK1以GTP作为磷酸基供体对内质网跨膜蛋白INSIG1/2进行磷酸化,使其与细胞内脂质的结合出现障碍,进而促进SREBP信号通路的激活及肿瘤细胞的脂质合成。这有别于以往的以ATP作为磷酸基供体的蛋白激酶。同时研究也论述了PCK1的内质网易位是肿瘤细胞协同调节糖异生降低和脂质合成激活的重要分子机制揭示了肿瘤细胞脂质感应异常以及脂质合成持续激活的重要机制。

而在本综述论文中,吕志民教授系统总结并讨论了肿瘤细胞中脂质(脂肪酸和胆固醇)摄取、脂肪生成和FAO依赖性脂解的相关研究进展,并详细介绍了肿瘤细胞中脂肪生成的转录调控。在文章最后,吕志民教授还讨论了通过破坏脂质代谢以用于肿瘤治疗的不同方法。

肿瘤脂质合成代谢分子调控网络(摘自综述)

原始出处:

Xueli Bian, Rui Liu, Ying Meng, et al. Lipid metabolism and cancer .J Exp Med (2021) 218 (1): e20201606.https://doi.org/10.1084/jem.20201606. December 18 2020

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