Prabhakar Bellur S, Mulherkar Nirupama, Prasad Kanteti V
Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 60612, USA.
Clin Cancer Res. 2008 Jan 15;14(2):347-51. doi: 10.1158/1078-0432.CCR-07-0493.
Tumor necrosis factor receptor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis primarily in cancer cells with little or no effect on normal cells; therefore, it has the potential for use in cancer therapy. TRAIL binding to death receptors DR4 and DR5 triggers the death-inducing signal complex formation and activation of procaspase-8, which in turn activates caspase-3, leading to cell death. Like FasL, TRAIL can trigger type 1 (caspase-8 --> caspase-3) or type 2 (caspase-8 --> Bid cleavage --> capsase-9 --> caspase-3) apoptotic pathways depending on the cell type. Some cancers are resistant to TRAIL treatment because most molecules in the TRAIL signaling pathway, including FLIPs and IAPs, can contribute to resistance. In addition, we have identified an essential role for splice variants of the IG20 gene in TRAIL resistance.
肿瘤坏死因子受体相关凋亡诱导配体（TRAIL）主要可诱导癌细胞凋亡，对正常细胞几乎没有影响；因此，它具有用于癌症治疗的潜力。TRAIL与死亡受体DR4和DR5结合会触发死亡诱导信号复合物的形成并激活procaspase-8，procaspase-8进而激活caspase-3，导致细胞死亡。与FasL一样，TRAIL可根据细胞类型触发1型（caspase-8 --> caspase-3）或2型（caspase-8 --> Bid裂解 --> capsase-9 --> caspase-3）凋亡途径。一些癌症对TRAIL治疗具有抗性，因为TRAIL信号通路中的大多数分子，包括FLIPs和IAPs，都可能导致抗性。此外，我们已经确定IG20基因的剪接变体在TRAIL抗性中起重要作用。
