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A ZEB1-HDAC pathway enters the epithelial to mesenchymal transition world in pancreatic cancer
  1. Günter Schneider1,
  2. Oliver H Krämer2,
  3. Dieter Saur1
  1. 1II Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, München, Germany
  2. 2Friedrich-Schiller-University Jena, Center for Molecular Biomedicine, Institute of Biochemistry and Biophysics, Jena, Germany
  1. Correspondence to Dr Günter Schneider, Technical University of Munich, Klinikum rechts der Isar, II. Medizinische Klinik, Ismaninger Str. 22, 81675 Munich, Germany; guenter.schneider{at}lrz.tum.de

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Epithelial to mesenchymal transition (EMT) correlates with high-grade malignancy including the competence to form metastases. In addition, EMT has recently been linked to cellular self-renewal programmes of cancer stem cells and apoptosis/anoikis resistance, which are all features of therapeutic resistance. The EMT programme is driven by several transcription factors (TFs), such as the transcriptional regulators SNAIL, SLUG, ZEB1 and ZEB2 and the basic helix–loop–helix factors E47 and TWIST. These proteins target and repress the CDH1 gene, which encodes for E-cadherin, an important caretaker of the epithelial state. Expression studies in human pancreatic cancer showed expression of SNAIL in 78% and of SLUG in 50% of cases.1 Although no or low levels of TWIST are expressed in pancreatic cancers, up-regulation of this gene under hypoxic condition may argue for a contribution towards tumour progression.1 2 Expression of the ZEB2 gene was recently found to be silenced by promoter methylation in the majority of pancreatic cancers. This finding argues against ZEB2 as a major repressor of E-cadherin in pancreatic cancer.3 In addition to such expression data, the functional relevance of SNAIL and SLUG for EMT and repression of the CDH1 gene has been described in various pancreatic cancer models in vitro and in vivo.4–7

Aghdassi et al (in press) present new compelling evidence that the zinc-finger TF ZEB1 is a repressor of E-cadherin expression.8 Based on the observation that 40% of pancreatic cancers have reduced E-cadherin levels and that low E-cadherin expression correlates with a poor prognosis …

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