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SUMMARY:Colon CSCs are sensitized by HDACinhibitors in a FOXO-dependent fa
 shion - Jan Paul Medema (Amsterdam Medical Center)
DTSTART:20130916T150000Z
DTEND:20130916T160000Z
UID:TALK44363@talks.cam.ac.uk
CONTACT:Florian Markowetz
DESCRIPTION:Cancer Stem Cells (CSC) display selective resistance towards c
 hemotherapy and are thought to be the cause of therapy failure. In this st
 udy we explored the underlying mechanisms using a Wnt-reporter construct t
 o identify CSC. We observed that high Wnt activity functionally designates
  the colon CSC population. Moreover\, in primary cancers the tumor cells w
 ith high Wnt pathway activity are preferentially localized close to stroma
 l myofibroblasts and derive HGF-dependent signals from the microenvironmen
 t. Using an in vitro chemotherapy analysis we observed that CSCs are selec
 tively resistant to chemotherapy. This resistance can be circumvented by p
 retreatment with HDAC inhibitors\, which change the level of pro and anti-
 apoptotic molecules and thereby facilitate cell death. Importantly\, treat
 ment with HDAC inhibitors results in a strong reduction of typical stem ce
 ll markers and shows strong induction of differentiation. HDAC inhibitors 
 therefore pose a novel means to sensitize CSC to therapy by enhancing thei
 r differentiation. Mechanistic insight into this mechanism and the role of
  FOXO transcription factors will be presented.
LOCATION:Cancer Research UK Cambridge Institute\, Lecture Theatre
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