Peter Marcus E
Northwestern University; Feinberg School of Medicine; Division Hematology/Oncology; Chicago, IL USA.
Cell Cycle. 2014;13(9):1373-8. doi: 10.4161/cc.28673. Epub 2014 Apr 1.
The conventional view of CD95 (Fas/APO-1) is that it is a dedicated apoptosis-inducing receptor with important functions in immune cell homeostasis and in viral and tumor defense. There is an emerging recognition, however, that CD95 also has multiple non-apoptotic activities. In the context of cancer, CD95 was shown to have tumor-promoting activities, and the concept of this new function of CD95 in cancer is gaining traction. Recently, we showed that not only is CD95 a growth promoter for cancer cells, but, paradoxically, when either CD95 or CD95 ligand (CD95L) is removed, that virtually all cancer cells die through a process we have named DICE (death induced by CD95R/L elimination). In this perspective, I outline a hypothesis regarding the physiological function of DICE, and why it may be possible to use induction of DICE to treat many, if not most, cancers.
传统观点认为，CD95（Fas/APO-1）是一种专门的凋亡诱导受体，在免疫细胞稳态以及病毒和肿瘤防御中具有重要功能。然而，人们逐渐认识到，CD95还具有多种非凋亡活性。在癌症背景下，CD95已被证明具有促肿瘤活性，并且CD95在癌症中的这一新功能概念正越来越受到关注。最近，我们发现CD95不仅是癌细胞的生长促进因子，而且自相矛盾的是，当去除CD95或CD95配体（CD95L）时，几乎所有癌细胞都会通过我们命名为DICE（CD95R/L消除诱导的死亡）的过程死亡。从这个角度出发，我概述了一个关于DICE生理功能的假设，以及为什么有可能利用DICE诱导来治疗许多（如果不是大多数）癌症。
