Fatty acid addiction in cancer: A high-fat diet directly promotes tumor growth through fatty acid oxidation

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer Pub Date : 2025-08-20 DOI:10.1016/j.bbcan.2025.189428

Soo-Youl Kim

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引用次数: 0

Abstract

Tumor growth promoted by a high-fat diet (HFD) was completely reversed by inhibiting fatty acid oxidation (FAO). The promotion of tumors by an HFD is known to result from the indirect effects of sex hormones, leptin, and adipokines such as insulin-like growth factor-1 (IGF-1) on cancer cells. However, even though HFD notably increased blood levels of IGF-1, knocking down the carnitine-acylcarnitine carrier (CAC) to inhibit FAO completely reversed the tumor-promoting effects in pancreatic cancer cells, accompanied by a significant decrease in ATP production. When ATP levels dropped due to FAO inhibition in cancer cells, mTOR – a key regulator of survival - became inactive, leading to reduced cell viability and increased cell death. This shows that HFD promotes cancer cell growth by supplying more calories through FAO, indicating that cancer is addicted to fatty acids. This review emphasizes the crucial role of cancer-specific FAO in tumor growth and proposes potential new therapeutic strategies targeting various FAO enzymes as innovative anti-cancer treatments.

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癌症中的脂肪酸成瘾：高脂肪饮食通过脂肪酸氧化直接促进肿瘤生长

通过抑制脂肪酸氧化（FAO），高脂肪饮食（HFD）促进的肿瘤生长完全逆转。已知HFD促进肿瘤是由于性激素、瘦素和脂肪因子如胰岛素样生长因子-1 （IGF-1）对癌细胞的间接作用。然而，尽管HFD显著提高了血液中IGF-1的水平，但通过抑制肉毒碱-酰基肉毒碱载体（CAC）来抑制FAO，完全逆转了胰腺癌细胞的促瘤作用，同时显著减少了ATP的产生。当肿瘤细胞中ATP水平因FAO抑制而下降时，mTOR（存活的关键调节因子）变得不活跃，导致细胞活力降低和细胞死亡增加。这表明HFD通过提供更多的卡路里来促进癌细胞生长，表明癌症对脂肪酸上瘾。这篇综述强调了癌症特异性FAO在肿瘤生长中的关键作用，并提出了针对各种FAO酶的潜在新治疗策略，作为创新的抗癌治疗方法。

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来源期刊

Biochimica et biophysica acta. Reviews on cancer 医学-生化与分子生物学

CiteScore

17.20

自引率

0.00%

发文量

138

审稿时长

33 days

期刊介绍： Biochimica et Biophysica Acta (BBA) - Reviews on Cancer encompasses the entirety of cancer biology and biochemistry, emphasizing oncogenes and tumor suppressor genes, growth-related cell cycle control signaling, carcinogenesis mechanisms, cell transformation, immunologic control mechanisms, genetics of human (mammalian) cancer, control of cell proliferation, genetic and molecular control of organismic development, rational anti-tumor drug design. It publishes mini-reviews and full reviews.