Title
Stat3 controls lysosomal-mediated cell death in vivo
Abbreviated Journal Title
Nat. Cell Biol.
Keywords
MAMMARY-GLAND INVOLUTION; TUMOR-NECROSIS-FACTOR; EPITHELIAL-CELLS; KAPPA-B; CASPASE ACTIVATION; GENE-EXPRESSION; DOWN-REGULATION; APOPTOSIS; CATHEPSIN; PATHWAY; Cell Biology
Abstract
It is well established that lysosomes play an active role during the execution of cell death(1). A range of stimuli can lead to lysosomal membrane permeabilization (LMP), thus inducing programmed cell death without involvement of the classical apoptotic programme(2,3). However, these lysosomal pathways of cell death have mostly been described in vitro or under pathological conditions(4-7). 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(1,9,10).
Journal Title
Nature Cell Biology
Volume
13
Issue/Number
3
Publication Date
1-1-2011
Document Type
Article
DOI Link
Language
English
First Page
303
Last Page
U263
WOS Identifier
ISSN
1465-7392
Recommended Citation
"Stat3 controls lysosomal-mediated cell death in vivo" (2011). Faculty Bibliography 2010s. 1507.
https://stars.library.ucf.edu/facultybib2010/1507
Comments
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