Nature Metabolism:揭开癌细胞依赖脂肪摄入之谜,减少脂肪摄入可缓解肿瘤生长

2022-06-29 王聪 生物世界

这项研究揭示了癌细胞需要摄入脂质的原因,同时也发现了癌细胞的脆弱之处,减少脂肪摄入量可能会减缓甚至阻止癌症的生长,这一发现为癌症治疗带来了新的思路和方法。

当缺乏氧气(缺氧)时,健康细胞的生长会受到限制。但缺氧却是90%的实体瘤中广泛存在的一种特征,而且缺氧这种特征与癌细胞的增殖、分化、血管生成、能量代谢以及癌症的耐药性发生、患者预后较差密切相关。

近日,美国哥伦比亚大学、麻省理工学院等机构的研究人员在 Nature 子刊 Nature Metabolism 发表了题为:Cancer cells depend on environmental lipids for proliferation when electron acceptors are limited 的研究论文。

癌细胞的的快速分裂需要大量脂质用于构成新细胞的细胞膜,而脂质的从头合成需要大量消耗 NAD+,癌细胞所处的缺氧环境限制了 NAD+ 的产生,因此,癌细胞需要绕过 NAD+,直接吸收摄入的脂质,用于癌细胞的分裂和生长。

这项研究揭示了癌细胞需要摄入脂质的原因,同时也发现了癌细胞的脆弱之处,减少脂肪摄入量可能会减缓甚至阻止癌症的生长,这一发现为癌症治疗带来了新的思路和方法。

细胞通过呼吸作用消耗氧气来产生能量。这也是为什么我们在运动时会加快呼吸。但癌细胞通常处于缺氧环境中,因此人们认为癌细胞的生长通常受到能量的限制。

除了直接通过呼吸作用功能外,氧气还作为氧化剂为化学反应提供氧化动力,驱动合成新细胞所必须的分子。许多生物合成反应都需要一种名为 NAD+ 的辅助因子,当缺氧时,细胞无法再生促进生长的 NAD+,并导致许多关键生物合成反应停止。

在这项最新研究中,研究团队惊讶地发现,缺氧的癌细胞通常具有比它们生长所需的更多的能量,当为这些癌细胞提供额外的营养来产生能量时,癌细胞并没有反应。相反,当研究团队使用各种方法来恢复因缺氧而被抑制的生物合成途径时,癌细胞的增殖能力大幅增加。

研究团队发现,虽然细胞内的各种生物合成途径对氧气供应都很敏感,但脂肪的合成受到缺氧的影响最大。脂肪是细胞膜的重要组成部分,因此,脂肪的合成对于旺盛分裂、不断需要新的细胞膜的癌细胞来说至关重要。缺氧条件下,细胞就无法充分供应其脂肪生物合成途径。

该研究的通讯作者、哥伦比亚大学的 Dennis Vitkup 副教授表示,这项研究结果非常反直觉,因为之前认为脂肪合成不是一个需要大量氧气的过程,但这项研究显示,癌细胞使用了高达30%的氧气用于合成脂肪,而不是用来产能。

由于氧气对生物合成途径的重要影响,在缺氧环境中生长的癌细胞强烈依赖于从环境中摄入脂肪。这也为癌细胞带来了一个至关重要的脆弱之处——减少脂肪摄入量可能会减缓甚至阻止癌症的生长。

该研究还表明,改变饮食中脂肪的成分可能在影响癌症生长方面发挥着至关重要的作用。研究团队正在进一步寻找不同肿瘤中癌细胞用来输入脂肪的受体,以及哪些受体可以被药物靶向。

Dennis Vitkup 表示,通常认为癌症主要是由基因突变所驱动的,但这项研究进一步指出,对于生活在缺氧环境中的癌细胞来说,环境本身同样重要。

 

原始出处:

Li, Z., Ji, B.W., Dixit, P.D. et al. Cancer cells depend on environmental lipids for proliferation when electron acceptors are limited. Nat Metab 4, 711–723 (2022). https://doi.org/10.1038/s42255-022-00588-8.

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    2022-09-22 liye789132251
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    2023-01-17 guojianrong
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    2023-05-29 一闲
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    2022-06-30 yxch36
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    2022-06-30 闆锋旦

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