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SUMMARY:Stat3: The Secret Ingredient to turn Lysosomes deadly? - Peter Kre
 uzaler\, Dept of Pathology\, University of Cambridge
DTSTART:20110608T113000Z
DTEND:20110608T123000Z
UID:TALK30775@talks.cam.ac.uk
CONTACT:Sue Griffin
DESCRIPTION:In recent years the classic subdivision of apoptotic (programm
 ed) cell death on one side and necrotic (accidental) cell death on the oth
 er has been enriched by an ever growing number of alternative pathways of 
 cell death that can act in conjunction with or independently from apoptosi
 s. \n\nAmongst these alternative pathways of cell death\, the lysosomal me
 diated pathway\, which relies on partial lysosomal membrane permeabilizati
 on (LMP)\, has elicited increasing interest. Nevertheless\, this type of c
 ell death was believed to be confined to pathological conditions such as t
 umour cells or neurons after brain injury\, and was seen as a backup mecha
 nism when classical apoptosis fails to be activated.\n\nContrary to this v
 iew\, recent findings from our group have shown that the regression of the
  mammary gland after lactation (involution)\, is carried out by non-classi
 cal\, executioner caspase independent\, lysosomal mediated programmed cell
  death (LM-PCD). This is the first time LM-PCD has been described under ph
 ysiological circumstances. Furthermore we could show that Stat3 is indispe
 nsable for LM-PCD and regulates this pathway in at least two ways: 1) by u
 pregulating lysosomal proteases such as cathepsins\, while 2) downregulati
 ng the cytosolic cathepsin inhibitor Spi2A. Stat3 is also known to be comm
 only hyperactivated in breast cancers and is a marker of poor prognosis. W
 e thus studied the impact of active Stat3 on the size\, localisation and s
 tability of lysosomes.\n\nPreviously our group could show that during line
 age determination of the mammary gland several pathways known to be involv
 ed in lineage commitment of T-cells\, such as the IL4/IL13/Stat6 pathway\,
  have been hijacked by mammary epithelial cells. Interestingly further par
 allels can be found during the execution of cell death in involution. To s
 uit the occasion\, on the basis of these examples some common characterist
 ics of these two cellular systems will be discussed.   \n
LOCATION:Lecture Theatre\, Department of Pathology\, Tennis Court Road
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