Yazlovitskaya Eugenia M, Graham Todd R
Department of Biological Sciences, Vanderbilt University, Nashville, TN 37232, USA.
Cancers (Basel). 2023 Aug 30;15(17):4327. doi: 10.3390/cancers15174327.
Adaptations of cancer cells for survival are remarkable. One of the most significant properties of cancer cells to prevent the immune system response and resist chemotherapy is the altered lipid metabolism and resulting irregular cell membrane composition. The phospholipid distribution in the plasma membrane of normal animal cells is distinctly asymmetric. Lipid flippases are a family of enzymes regulating membrane asymmetry, and the main class of flippases are type IV P-type ATPases (P4-ATPases). Alteration in the function of flippases results in changes to membrane organization. For some lipids, such as phosphatidylserine, the changes are so drastic that they are considered cancer biomarkers. This review will analyze and discuss recent publications highlighting the role that P4-ATPases play in the development and progression of various cancer types, as well as prospects of targeting P4-ATPases for anti-cancer treatment.
癌细胞为存活而进行的适应性变化十分显著。癌细胞阻止免疫系统反应并抵抗化疗的最重要特性之一是脂质代谢改变以及由此导致的细胞膜组成异常。正常动物细胞质膜中的磷脂分布明显不对称。脂质翻转酶是一类调节膜不对称性的酶，其中主要的翻转酶类型是IV型P型ATP酶（P4-ATP酶）。翻转酶功能的改变会导致膜组织的变化。对于某些脂质，如磷脂酰丝氨酸，这种变化非常剧烈，以至于它们被视为癌症生物标志物。本综述将分析和讨论近期的出版物，这些出版物突出了P4-ATP酶在各种癌症类型的发生和发展中所起的作用，以及将P4-ATP酶作为抗癌治疗靶点的前景。
