Key Laboratory of Epigenetics and Oncology, Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, China.
Clinical Pharmacy Center, Department of Pharmacy, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
Front Immunol. 2022 Nov 17;13:1059376. doi: 10.3389/fimmu.2022.1059376. eCollection 2022.
ADAM17 is a member of the a disintegrin and metalloproteinase (ADAM) family of transmembrane proteases involved in the shedding of some cell membrane proteins and regulating various signaling pathways. More than 90 substrates are regulated by ADAM17, some of which are closely relevant to tumor formation and development. Besides, ADAM17 is also responsible for immune regulation and its substrate-mediated signal transduction. Recently, ADAM17 has been considered as a major target for the treatment of tumors and yet its immunomodulatory roles and mechanisms remain unclear. In this paper, we summarized the recent understanding of structure and several regulatory roles of ADAM17. Importantly, we highlighted the immunomodulatory roles of ADAM17 in tumor development, as well as small molecule inhibitors and monoclonal antibodies targeting ADAM17.
ADAM17 是解整合素金属蛋白酶(ADAM)家族的成员之一,该家族的跨膜蛋白酶参与了一些细胞膜蛋白的脱落,并调节各种信号通路。ADAM17 调节着超过 90 种底物,其中一些与肿瘤的形成和发展密切相关。此外,ADAM17 还负责免疫调节及其底物介导的信号转导。最近,ADAM17 已被认为是治疗肿瘤的主要靶点,但它的免疫调节作用和机制尚不清楚。本文总结了 ADAM17 的结构和几种调节作用的最新认识。重要的是,我们强调了 ADAM17 在肿瘤发展中的免疫调节作用,以及针对 ADAM17 的小分子抑制剂和单克隆抗体。