Zhang Zhiliang, Xiang Siqi, Cui Ruxia, Peng Hang, Mridul Roy, Xiang Mingjun
Department of Biochemistry and Immunology, Medical Research Center, Institute of Medicine, Jishou University, Jishou, China.
The State Ethnic Committee's Key Laboratory of Clinical Engineering Laboratory of Xiangxi Miao Pediatric Tuina, Jishou University, Jishou, China.
Front Oncol. 2022 Jun 23;12:922596. doi: 10.3389/fonc.2022.922596. eCollection 2022.
Inhibitor of apoptosis protein-related-like protein-2 (ILP-2), also known as BIRC-8, is a member of the inhibitor of apoptosis protein (IAPs) family, which mainly encodes the negative regulator of apoptosis. It is selectively overexpressed in a variety of human tumors and can help tumor cells evade apoptosis, promote tumor cell growth, increase tumor cell aggressiveness, and appears to be involved in tumor cell resistance to chemotherapeutic drugs. Several studies have shown that downregulation of ILP-2 expression increases apoptosis, inhibits metastasis, reduces cell growth potential, and sensitizes tumor cells to chemotherapeutic drugs. In addition, ILP-2 inhibits apoptosis in a unique manner; it does not directly inhibit the activity of caspases but induces apoptosis by cooperating with other apoptosis-related proteins. Here, we review the current understanding of the various roles of ILP-2 in the apoptotic cascade and explore the use of interfering ILP-2, and the combination of related anti-tumor agents, as a novel strategy for cancer therapy.
凋亡抑制蛋白相关样蛋白2(ILP-2),也称为BIRC-8,是凋亡抑制蛋白(IAPs)家族的成员,该家族主要编码凋亡的负调节因子。它在多种人类肿瘤中选择性过表达,可帮助肿瘤细胞逃避凋亡、促进肿瘤细胞生长、增加肿瘤细胞侵袭性,并且似乎参与肿瘤细胞对化疗药物的耐药性。多项研究表明,ILP-2表达下调可增加凋亡、抑制转移、降低细胞生长潜能,并使肿瘤细胞对化疗药物敏感。此外,ILP-2以独特的方式抑制凋亡;它不直接抑制半胱天冬酶的活性,而是通过与其他凋亡相关蛋白协同作用来诱导凋亡。在此,我们综述了目前对ILP-2在凋亡级联反应中各种作用的理解,并探讨干扰ILP-2以及联合相关抗肿瘤药物作为癌症治疗新策略的应用。