Document Detail

Stat3 controls lysosomal-mediated cell death in vivo.
MedLine Citation:
PMID:  21336304     Owner:  NLM     Status:  Publisher    
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.
Peter A Kreuzaler; Anna D Staniszewska; Wenjing Li; Nader Omidvar; Blandine Kedjouar; James Turkson; Valeria Poli; Richard A Flavell; Richard W E Clarkson; Christine J Watson
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-2-20
Journal Detail:
Title:  Nature cell biology     Volume:  -     ISSN:  1476-4679     ISO Abbreviation:  -     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-2-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100890575     Medline TA:  Nat Cell Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
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