Genome-wide analysis of the CUX1 transcriptional network mediating resistance to apoptosis in pancreatic cancer
Summary:
Previously, we identified the transcription factor CUX1 as important enhancer of tumor progression and resistance to drug-induced
apoptosis in pancreatic cancer, and identified several CUX1 target genes mediating the effects of CUX1, among them the secreted Wnt
ligand WNT5A. Aim of the first KFO210 funding period was to elucidate effector pathways within the CUX1 transcriptional network
with particular focus on WNT5A. The project proposed now aims to decipher the CUX1-induced transcriptional network affecting
drug resistance systematically using a genome-wide approach. For that purpose, we will employ chromatin-immunoprecipitation (ChIP)
followed by subsequent next-generation sequencing (ChIP-seq). The resulting promoter sequences will be individually validated and
characterized. In addition, CUX1 binding partners modulating CUX1-induced resistance to apoptosis will be isolated using tandem
affinity purification (TAP) technology and subsequent identification by mass spectroscopy. Target genes and partner proteins of
CUX1 identified by these techniques mediating drug resistance will be characterized in vitro and in vivo using xenografts and
genetic mouse models of pancreatic cancer.
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KLINISCHE FORSCHERGRUPPE 210 |
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