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Wnt/β-catenin 信号通路在肾上腺生理学和肿瘤发生发展中的作用。

Wnt/β-catenin signalling in adrenal physiology and tumour development.

机构信息

CNRS UMR6247, Génétique Reproduction et Développement, Clermont Université, Aubière, France.

出版信息

Mol Cell Endocrinol. 2012 Mar 31;351(1):87-95. doi: 10.1016/j.mce.2011.09.009. Epub 2011 Sep 10.

Abstract

Wnt/β-catenin signalling plays essential roles during embryonic development and in adult tissue homeostasis. Canonical signalling through Wnt secreted ligands relies on the control of β-catenin cytoplasmic accumulation and translocation to the nucleus. In this compartment, β-catenin serves as a transcription coactivator for transcription factors such as Lef/Tcf or some nuclear receptors. Constitutive Wnt signalling resulting from inactivation of inhibitors of the pathway or from activating mutations in β-catenin, triggers tumour development in a number of tissues. Analysis of patients' samples and genetically engineered mouse models has shown that Wnt signalling was involved in adrenal development and tumourigenesis. This review will summarise all these recent findings and will focus on some of the mechanisms that may lead to aberrant accumulation of β-catenin in adrenocortical tumours.

摘要

Wnt/β-catenin 信号通路在胚胎发育和成人组织稳态中发挥着重要作用。Wnt 分泌配体的经典信号通路依赖于对 β-catenin 细胞质积累和核转位的控制。在这个隔间中,β-catenin 作为转录因子如 Lef/Tcf 或一些核受体的转录共激活因子。由于途径抑制剂的失活或 β-catenin 的激活突变导致的组成性 Wnt 信号通路触发了许多组织中的肿瘤发生。对患者样本和基因工程小鼠模型的分析表明,Wnt 信号通路参与了肾上腺发育和肿瘤发生。这篇综述将总结所有这些最新发现,并将重点介绍一些可能导致肾上腺皮质肿瘤中β-catenin 异常积累的机制。

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