Lee Jaewang, Shin Daiha, Roh Jong-Lyel
Department of Otorhinolaryngology-Head and Neck Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea.
Western Seoul Center, Korea Basic Science Institute, Seoul, Republic of Korea.
Eur J Pharmacol. 2023 Feb 15;941:175497. doi: 10.1016/j.ejphar.2023.175497. Epub 2023 Jan 6.
Cancer often perturbs lipid metabolism, which leads to the alteration of metabolism intermediates, contributing to their deregulated growth and metastasis. Alteration of lipid metabolism shifting to contain more polyunsaturated fatty acids (PUFAs) in membrane phospholipids (PLs) also leads to cancer therapy resistance. High amounts of PL-PUFAs render cancer cells more vulnerable to lipid peroxidation (LPO), predisposing them towards ferroptosis, a new form of iron-dependent oxidative regulated cell death. The commitment of cancer undergoing ferroptotic cell death depends on the adaptive lipidome remodeling, LPO patterns, and LPO scavenging ability in heterogeneous cancer cells. Ferroptosis is receiving attention in cancer research as treating cancers, altering membrane lipid homeostasis, and refractory from conventional therapies. Therefore, a better understanding of the molecular underpinning of lipid metabolism alterations may provide new opportunities for solving cancer resistance. This review intends to understand altered lipid metabolism in cancers and discuss lipid composition and metabolic processes associated with ferroptosis induction in cancers.
癌症常常扰乱脂质代谢，这会导致代谢中间体发生改变，促使癌细胞生长失控并发生转移。脂质代谢的改变使膜磷脂（PL）中含有更多的多不饱和脂肪酸（PUFA），这也会导致癌症治疗耐药性。大量的PL-PUFA使癌细胞更容易发生脂质过氧化（LPO），从而使其倾向于发生铁死亡，这是一种新的铁依赖性氧化调节细胞死亡形式。癌症发生铁死亡细胞死亡的过程取决于异质性癌细胞中适应性脂质组重塑、LPO模式和LPO清除能力。铁死亡在癌症研究中受到关注，因为它可用于治疗癌症、改变膜脂质稳态以及克服传统疗法的耐药性。因此，更好地理解脂质代谢改变的分子基础可能为解决癌症耐药性提供新的机会。本综述旨在了解癌症中脂质代谢的改变，并讨论与癌症中铁死亡诱导相关的脂质组成和代谢过程。
