School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
Department of Surgery, College of Medicine, Seoul National University, Seoul, South Korea.
Adv Exp Med Biol. 2021;1187:23-52. doi: 10.1007/978-981-32-9620-6_2.
Breast cancer progression results from subversion of multiple intra- or intercellular signaling pathways in normal mammary tissues and their microenvironment, which have an impact on cell differentiation, proliferation, migration, and angiogenesis. Phospholipases (PLC, PLD and PLA) are essential mediators of intra- and intercellular signaling. They hydrolyze phospholipids, which are major components of cell membrane that can generate many bioactive lipid mediators, such as diacylglycerol, phosphatidic acid, lysophosphatidic acid, and arachidonic acid. Enzymatic processing of phospholipids by phospholipases converts these molecules into lipid mediators that regulate multiple cellular processes, which in turn can promote breast cancer progression. Thus, dysregulation of phospholipases contributes to a number of human diseases, including cancer. This review describes how phospholipases regulate multiple cancer-associated cellular processes, and the interplay among different phospholipases in breast cancer. A thorough understanding of the breast cancer-associated signaling networks of phospholipases is necessary to determine whether these enzymes are potential targets for innovative therapeutic strategies.
乳腺癌的进展源于正常乳腺组织及其微环境中多个细胞内或细胞间信号通路的颠覆,这些信号通路会影响细胞分化、增殖、迁移和血管生成。磷脂酶(PLC、PLD 和 PLA)是细胞内和细胞间信号转导的重要介质。它们可以水解磷脂,磷脂是细胞膜的主要成分,能够生成许多生物活性脂质介质,如二酰基甘油、磷酸脂酸、溶血磷脂酸和花生四烯酸。磷脂酶对磷脂的酶促处理将这些分子转化为调节多种细胞过程的脂质介质,从而促进乳腺癌的进展。因此,磷脂酶的失调会导致许多人类疾病,包括癌症。本文描述了磷脂酶如何调节多种与癌症相关的细胞过程,以及在乳腺癌中不同磷脂酶之间的相互作用。深入了解与乳腺癌相关的磷脂酶信号网络,对于确定这些酶是否是创新治疗策略的潜在靶点是必要的。