The WNT/β‐catenin dependent transcription: A tissue‐specific business

Abstract

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

FOS Rescues Neuronal Differentiation of Sox2-Deleted Neural Stem Cells by Genome-Wide Regulation of Common SOX2 and AP1(FOS-JUN) Target Genes

“…Notably, it is precisely during mesoderm formation that one of the best-documented cases of the SOX-WNT interactions occurs, exemplified by the SOX17 genome-wide co-occupancy with β-catenin [ 52 ]. This indicates that the SOX factors might govern the tissue-specific action of Wnt signaling not only in embryonic stem cells or neural progenitors, but more in general during development [ 53 ].…”

Wnt/β-Catenin Signaling as a Driver of Hepatocellular Carcinoma Progression: An Emphasis on Molecular Pathways

“…45 Normally, β-catenin is present in cytoplasmic side of adherence junctions in epithelial cells with close contact with cadherins complex. 46 However, cytoplasmic βcatenin undergoes ubiquitination to be degraded by proteasomal route. 47,48 Therefore, the first impact of Wnt ligands is to enhance stability of β-catenin protein and prevent its degradation.…”

The interaction of canonical Wnt/β-catenin signaling with protein lysine acetylation

“…As mentioned, after Wnt/β-catenin signaling sensitization, β-catenin can interact with and activate TCF/LEF, which is also controlled by various transcriptional coregulators, including the coactivators and corepressors, at the target gene promoter in the cell nucleus [ 46 , 47 ]. Without Wnt signals, TCF/LEF binds to HDAC1 and HDAC2, and causes histone H3 hypo-acetylation at the promoters of Wnt-dependent genes, and induces suppression of gene transcription [ 48 – 51 ].…”