Department of Biochemistry and Molecular Biology (R.B., M.D., W.W.) and Department of Microbiology and Environmental Technology, Institute of Engineering and Environmental Protection (A.P.), University of Bielsko-Biala, Bielsko-Biala, Poland; and Department of Research and Development, Transfusion Center Bayreuth, Bayreuth, Germany (M.P.)
Department of Biochemistry and Molecular Biology (R.B., M.D., W.W.) and Department of Microbiology and Environmental Technology, Institute of Engineering and Environmental Protection (A.P.), University of Bielsko-Biala, Bielsko-Biala, Poland; and Department of Research and Development, Transfusion Center Bayreuth, Bayreuth, Germany (M.P.).
Mol Pharmacol. 2023 Mar;103(3):132-144. doi: 10.1124/molpharm.122.000607. Epub 2022 Dec 8.
To maintain their growth rate, cancer cells must secure a supply of fatty acids, which are necessary for building cell membranes and maintaining energy processes. This is one of the reasons why tissues with intensive fatty acid metabolism, such as the mammary gland, are more likely to develop tumors. One natural or induced defense process against cancer is ferroptosis, which interferes with normal fatty acid metabolism. This leads to the oxidation of polyunsaturated fatty acids, which causes a rearrangement of the metabolism and damages cell membranes. As a consequence of this oxidation, there is a shortage of normal polyunsaturated fatty acids, which disturbs the complicated metabolism of fatty acids. This imbalance in metabolism, resulting from the deficiency of properly structured fatty acids, is called, by these authors, "acyl starvation." When cancer cells are exposed to alternating hypoxia and reoxygenation, they often develop resistance to neoadjuvant therapies. Blocking the stearoyl-CoA desaturase - fatty acid-binding protein 4 - fatty acid translocase axis appears to be a promising pathway in the treatment of breast cancer. On the one hand, the inhibition of desaturase leads to the formation of toxic phospholipid hydroperoxides in ferroptosis, whereas on the other hand, the inhibition of fatty acid-binding protein 4 and translocase leads to a reduced uptake of fatty acids and disruption of the cellular transport of fatty acids, resulting in intracellular acyl starvation. The disruption in the metabolism of fatty acids in cancer cells may augment the effectiveness of neoadjuvant therapy. SIGNIFICANCE STATEMENT: Regulation of the metabolism of fatty acids in cancer cells seems to be a promising therapeutic direction. Studies show that the induction of ferroptosis in cancer cells, combined with use of neoadjuvant therapies, effectively inhibits the proliferation of these cells. We link the process of ferroptosis with apoptosis and SCD1-FABP4-CD36 axis and propose the term "acyl starvation" for the processes leading to FA deficiency, dysregulation of FA metabolism in cancer cells, and, most importantly, the appearance of incorrect proportions FAs.
为了保持其生长速度，癌细胞必须确保脂肪酸的供应，因为脂肪酸是构建细胞膜和维持能量过程所必需的。这就是为什么像乳腺这样脂肪酸代谢旺盛的组织更容易发生肿瘤的原因之一。一种针对癌症的自然或诱导防御过程是铁死亡，它会干扰正常的脂肪酸代谢。这导致多不饱和脂肪酸的氧化，从而导致代谢的重新排列和细胞膜的损伤。由于这种氧化，正常的多不饱和脂肪酸短缺，扰乱了脂肪酸的复杂代谢。这些作者将这种脂肪酸代谢的不平衡称为“酰基饥饿”，因为缺乏适当结构的脂肪酸。当癌细胞暴露于交替的缺氧和再氧化时，它们通常会对新辅助治疗产生耐药性。阻断硬脂酰辅酶 A 去饱和酶-脂肪酸结合蛋白 4-脂肪酸转运蛋白轴似乎是治疗乳腺癌的一种有前途的途径。一方面，去饱和酶的抑制导致铁死亡中有毒磷脂氢过氧化物的形成，另一方面，脂肪酸结合蛋白 4 和转运蛋白的抑制导致脂肪酸摄取减少和细胞内脂肪酸转运中断，导致细胞内酰基饥饿。脂肪酸代谢在癌细胞中的破坏可能会增强新辅助治疗的效果。意义声明：调节癌细胞中脂肪酸的代谢似乎是一种很有前途的治疗方向。研究表明，在癌细胞中诱导铁死亡，并结合使用新辅助治疗，可有效抑制这些细胞的增殖。我们将铁死亡过程与细胞凋亡和 SCD1-FABP4-CD36 轴联系起来，并提出“酰基饥饿”这个术语，用于描述导致 FA 缺乏、癌细胞中 FA 代谢失调以及最重要的是出现错误比例 FA 的过程。
