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首页> 外文期刊>Gut: Journal of the British Society of Gastroenterology >A ZEB1-HDAC pathway enters the epithelial to mesenchymal transition world in pancreatic cancer
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A ZEB1-HDAC pathway enters the epithelial to mesenchymal transition world in pancreatic cancer

机译：ZEB1-HDAC通路进入胰腺癌的上皮向间质转化世界

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摘要

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.Expression of the ZEBZ gene was recently found to be silenced by promoter meth-ylation in the majority of pancreatic cancers. This finding argues against ZEB2 as a major repressor of E-cadherin in pancreatic cancer. 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.
机译：上皮到间质转化（EMT）与高级别恶性肿瘤相关，包括形成转移的能力。此外，EMT最近已与癌症干细胞的细胞自我更新程序和凋亡/失语症抗性联系在一起，这些都是治疗性抗性的特征。 EMT程序由几个转录因子（TF）驱动，例如转录调节因子SNAIL，SLUG，ZEB1和ZEB2以及基本的螺旋-环螺旋因子E47和TWIST。这些蛋白质靶向并抑制CDH1基因，该基因编码上皮状态的重要看守者E-钙粘着蛋白。在人类胰腺癌中的表达研究表明，SNAIL的表达占78％，SLUG的表达占50％。1尽管胰腺癌中未表达TWIST或表达水平很低，但在低氧条件下该基因的上调可能表明有贡献最近发现在大多数胰腺癌中，ZEBZ基因的表达被启动子甲基化所沉默。这一发现反对ZEB2是胰腺癌中E-钙粘蛋白的主要阻遏物。除了这样的表达数据外，在各种胰腺癌模型中体外和体内还描述了SNAIL和SLUG与EMT的功能相关性以及CDH1基因的抑制。

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