期刊
CELL DEATH & DISEASE
卷 12, 期 11, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41419-021-04306-2
关键词
-
类别
Fin56 induces ferroptosis and autophagy in bladder cancer cells, with ferroptosis mechanistically depending on the autophagic machinery. Inhibition of autophagy at different stages attenuates Fin56-induced oxidative stress and GPX4 degradation. Additionally, the combination of Fin56 and Torin 2 synergistically enhances cytotoxicity against bladder cancer cells. The findings suggest that the crosstalk between ferroptosis and autophagy, along with the use of mTOR inhibitors, may offer a promising therapeutic strategy for bladder cancer.
Ferroptosis is a form of regulated cell death that emerges to be relevant for therapy-resistant and dedifferentiating cancers. Although several lines of evidence suggest that ferroptosis is a type of autophagy-dependent cell death, the underlying molecular mechanisms remain unclear. Fin56, a type 3 ferroptosis inducer, triggers ferroptosis by promoting glutathione peroxidase 4 (GPX4) protein degradation via a not fully understood pathway. Here, we determined that Fin56 induces ferroptosis and autophagy in bladder cancer cells and that Fin56-triggered ferroptosis mechanistically depends on the autophagic machinery. Furthermore, we found that autophagy inhibition at different stages attenuates Fin56-induced oxidative stress and GPX4 degradation. Moreover, we investigated the effects of Fin56 in combination with Torin 2, a potent mTOR inhibitor used to activate autophagy, on cell viability. We found that Fin56 synergizes with Torin 2 in cytotoxicity against bladder cancer cells. Collectively, our findings not only support the concept that ferroptosis is a type of autophagy-dependent cell death but imply that the combined application of ferroptosis inducers and mTOR inhibitors is a promising approach to improve therapeutic options in the treatment of bladder cancer.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据