Wallenberg Centre for Molecular Medicine, Linköping University, Linköping, Sweden.
Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology, Faculty of Health Science, Linköping University, Linköping, Sweden.
WIREs Mech Dis. 2021 May;13(3):e1511. doi: 10.1002/wsbm.1511. Epub 2020 Oct 21.
β-catenin-mediated Wnt signaling is an ancient cell-communication pathway in which β-catenin drives the expression of certain genes as a consequence of the trigger given by extracellular WNT molecules. The events occurring from signal to transcription are evolutionarily conserved, and their final output orchestrates countless processes during embryonic development and tissue homeostasis. Importantly, a dysfunctional Wnt/β-catenin pathway causes developmental malformations, and its aberrant activation is the root of several types of cancer. A rich literature describes the multitude of nuclear players that cooperate with β-catenin to generate a transcriptional program. However, a unified theory of how β-catenin drives target gene expression is still missing. We will discuss two types of β-catenin interactors: transcription factors that allow β-catenin to localize at target regions on the DNA, and transcriptional co-factors that ultimately activate gene expression. In contrast to the presumed universality of β-catenin's action, the ensemble of available evidence suggests a view in which β-catenin drives a complex system of responses in different cells and tissues. A malleable armamentarium of players might interact with β-catenin in order to activate the right "canonical" targets in each tissue, developmental stage, or disease context. Discovering the mechanism by which each tissue-specific β-catenin response is executed will be crucial to comprehend how a seemingly universal pathway fosters a wide spectrum of processes during development and homeostasis. Perhaps more importantly, this could ultimately inform us about which are the tumor-specific components that need to be targeted to dampen the activity of oncogenic β-catenin. This article is categorized under: Cancer > Molecular and Cellular Physiology Cancer > Genetics/Genomics/Epigenetics Cancer > Stem Cells and Development.
β-连环蛋白介导的 Wnt 信号通路是一种古老的细胞通讯途径，其中β-连环蛋白作为细胞外 WNT 分子触发的结果，驱动某些基因的表达。从信号到转录发生的事件在进化上是保守的，其最终输出在胚胎发育和组织稳态过程中协调着无数的过程。重要的是，功能失调的 Wnt/β-连环蛋白途径会导致发育畸形，其异常激活是多种类型癌症的根源。大量文献描述了与β-连环蛋白合作生成转录程序的多种核内参与者。然而，β-连环蛋白如何驱动靶基因表达的统一理论仍然缺失。我们将讨论两种类型的β-连环蛋白相互作用蛋白：允许β-连环蛋白在 DNA 上的靶区域定位的转录因子，以及最终激活基因表达的转录共因子。与β-连环蛋白作用的假定普遍性相反，现有的大量证据表明，β-连环蛋白在不同的细胞和组织中驱动一种复杂的反应系统。一套可塑的参与者可能与β-连环蛋白相互作用，以便在每种组织、发育阶段或疾病环境中激活正确的“经典”靶标。发现每个组织特异性β-连环蛋白反应的执行机制对于理解看似普遍的途径如何在发育和稳态过程中促进广泛的过程将是至关重要的。也许更重要的是，这最终可以告诉我们哪些是肿瘤特异性的成分，需要靶向这些成分以抑制致癌β-连环蛋白的活性。本文属于以下分类：癌症 > 分子和细胞生理学癌症 > 遗传学/基因组学/表观遗传学癌症 > 干细胞和发育。
