Intestinal Wnt in the transition from physiology to oncology

Abstract

Adult stem cells are necessary for self-renewal tissues and regeneration after damage. Especially in the intestine, which self-renews every few days, they play a key role in tissue homeostasis. Therefore, complex regulatory mechanisms are needed to prevent hyperproliferation, which can lead in the worst case to carcinogenesis or under-activation of stem cells, which can result in dysfunctional epithelial. One main regulatory signaling pathway is the Wnt/β-catenin signaling pathway. It is a highly conserved pathway, with β-catenin, a transcription factor, as target protein. Translocation of β-catenin from cytoplasm to nucleus activates the transcription of numerous genes involved in regulating stem cell pluripo-tency, proliferation, cell differentiation and regulation of cell death. This review presents a brief overview of the Wnt/β-catenin signaling pathway, the regulatory mechanism of this pathway and its role in intestinal homeostasis. Additionally, this review highlights the molecular mechanisms and the histomorphological features of Wnt hyperactivation. Furthermore, the central role of the Wnt signaling pathway in intestinal carcinogenesis as well as its clinical relevance in colorectal carcinoma are discussed.

β-catenin inhibitors in cancer therapeutics: intricacies and way forward

“…Following this, recruitment of the β-catenin ‘enhanceosome’ which includes BCL9, CBP, Pygopus, BRG1, etc., is observed [ 37 ]. Once activated, the transcriptional output of this complex includes c-Myc, CCND1, CDKN1A, cyclin D1, and Bcl-w, which are known to play critical roles in the process of carcinogenesis [ 38 ]. β-catenin can also interact with numerous other transcription factors like FOXO, HIF1, Sox family members, nuclear receptors, etc.…”