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

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.