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首页> 外文期刊>Nature cell biology >Stat3 controls lysosomal-mediated cell death in vivo.
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Stat3 controls lysosomal-mediated cell death in vivo.

机译：Stat3控制体内溶酶体介导的细胞死亡。

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It is well established that lysosomes play an active role during the execution of cell death. A range of stimuli can lead to lysosomal membrane permeabilization (LMP), thus inducing programmed cell death without involvement of the classical apoptotic programme. However, these lysosomal pathways of cell death have mostly been described in vitro or under pathological conditions. Here we show that the physiological process of post-lactational regression of the mammary gland is accomplished through a non-classical, lysosomal-mediated pathway of cell death. We found that, during involution, lysosomes in the mammary epithelium undergo widespread LMP. Furthermore, although cell death through LMP is independent of executioner caspases 3, 6 and 7, it requires Stat3, which upregulates the expression of lysosomal proteases cathepsin B and L, while downregulating their endogenous inhibitor Spi2A (ref. 8). Our findings report a previously unknown, Stat3-regulated lysosomal-mediated pathway of cell death under physiological circumstances. We anticipate that these findings will be of major importance in the design of treatments for cancers such as breast, colon and liver, where cathepsins and Stat3 are commonly overexpressed and/or hyperactivated respectively.
机译：众所周知，溶酶体在细胞死亡的执行过程中起着积极的作用。一系列刺激可导致溶酶体膜通透性（LMP），从而在不涉及经典凋亡程序的情况下诱发程序性细胞死亡。但是，这些细胞死亡的溶酶体途径主要是在体外或病理条件下描述的。在这里，我们显示了乳腺腺体后退性退化的生理过程是通过非经典的溶酶体介导的细胞死亡途径完成的。我们发现，在对合期间，乳腺上皮中的溶酶体会发生广泛的LMP。此外，尽管通过LMP引起的细胞死亡不依赖于敲除半胱氨酸蛋白酶3、6和7，但它需要Stat3，该酶上调溶酶体蛋白酶组织蛋白酶B和L的表达，同时下调其内源性抑制剂Spi2A（参考文献8）。我们的发现报告了生理条件下以前未知的，Stat3调控的溶酶体介导的细胞死亡途径。我们预计，这些发现在设计乳腺癌，结肠癌和肝癌的治疗方法中将具有重要意义，而其中组织蛋白酶和Stat3通常分别被过度表达和/或过度活化。

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