Jang Hyun-Jun, Suh Pann-Ghill, Lee Yu Jin, Shin Kyeong Jin, Cocco Lucio, Chae Young Chan
School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
Department of Biomedical and Neuromotor Sciences, Cellular Signalling Laboratory, Institute of Human Anatomy, University of Bologna, Bologna, Italy.
Adv Biol Regul. 2018 Jan;67:179-189. doi: 10.1016/j.jbior.2017.11.003. Epub 2017 Nov 8.
Phospholipase C (PLC) is an essential mediator of cellular signaling. PLC regulates multiple cellular processes by generating bioactive molecules such as inositol-1,4,5-triphosphate (IP) and diacylglycerol (DAG). These products propagate and regulate cellular signaling via calcium (Ca) mobilization and activation of protein kinase C (PKC), other kinases, and ion channels. PLCγ1, one of the primary subtypes of PLC, is directly activated by membrane receptors, including receptor tyrosine kinases (RTKs), and adhesion receptors such as integrin. PLCγ1 mediates signaling through direct interactions with other signaling molecules via SH domains, as well as its lipase activity. PLCγ1 is frequently enriched and mutated in various cancers, and is involved in the processes of tumorigenesis, including proliferation, migration, and invasion. Although many studies have suggested that PLCγ functions in cell mobility rather than proliferation in cancer, questions remain as to whether PLCγ regulates mitogenesis and whether PLCγ promotes or inhibits proliferation. Moreover, how PLCγ regulates cancer-associated cellular processes and the interplay among other proteins involved in cancer progression have yet to be fully elucidated. In this review, we discuss the current understanding of the role of PLCγ1 in cancer mobility and proliferation.
磷脂酶C(PLC)是细胞信号传导的重要介质。PLC通过生成生物活性分子如肌醇-1,4,5-三磷酸(IP)和二酰基甘油(DAG)来调节多种细胞过程。这些产物通过钙(Ca)动员以及蛋白激酶C(PKC)、其他激酶和离子通道的激活来传播和调节细胞信号传导。PLCγ1是PLC的主要亚型之一,可被膜受体直接激活,包括受体酪氨酸激酶(RTK)以及整合素等黏附受体。PLCγ1通过其SH结构域与其他信号分子的直接相互作用及其脂肪酶活性介导信号传导。PLCγ1在各种癌症中经常富集并发生突变,并参与肿瘤发生过程,包括增殖、迁移和侵袭。尽管许多研究表明PLCγ在癌症中作用于细胞迁移而非增殖,但关于PLCγ是否调节有丝分裂以及PLCγ促进还是抑制增殖仍存在疑问。此外,PLCγ如何调节癌症相关的细胞过程以及与癌症进展中涉及的其他蛋白质之间的相互作用尚未完全阐明。在本综述中,我们讨论了目前对PLCγ1在癌症迁移和增殖中作用的理解。