在没有底物附着的情况下，转移癌细胞可以发展出抗缺乏底物附着所引发的程序性细胞死亡（anoikis）并存活以对抗肿瘤。Anoikis是通过内溶酶体依赖和外源性死亡受体途径进行调控的。研究表明，caspase-8依赖的外部途径似乎比内部途径的活性更为重要。本文回顾了外部途径通过死亡受体介导的anoikis调控机制。不同的死亡受体与不同的配体结合，以激活下游caspases。本文还回顾了Fas结合Fas相关死亡域（FADD）和肿瘤坏死因子受体1结合炎症性细胞因子相关死亡域（TRADD），以及DR4和DR5结合FADD引发下游caspase活化并调控anoikis的可能机制。本文着重介绍了死亡受体途径介导的anoikis的可能机制，并为研究肿瘤转移机制提供了新的见解和研究方向。视频摘要。© 2023，BioMed Central Ltd.，Springer Nature的一部分。

Metastatic cancer cells can develop anoikis resistance in the absence of substrate attachment and survive to fight tumors. Anoikis is mediated by endogenous mitochondria-dependent and exogenous death receptor pathways, and studies have shown that caspase-8-dependent external pathways appear to be more important than the activity of the intrinsic pathways. This paper reviews the regulation of anoikis by external pathways mediated by death receptors. Different death receptors bind to different ligands to activate downstream caspases. The possible mechanisms of Fas-associated death domain (FADD) recruitment by Fas and TNF receptor 1 associated-death domain (TRADD) recruitment by tumor necrosis factor receptor 1 (TNFR1), and DR4- and DR5-associated FADD to induce downstream caspase activation and regulate anoikis were reviewed. This review highlights the possible mechanism of the death receptor pathway mediation of anoikis and provides new insights and research directions for studying tumor metastasis mechanisms. Video Abstract.© 2023. BioMed Central Ltd., part of Springer Nature.