WNT Signaling in Stem Cells: A Look into the Non-Canonical Pathway

Abstract

Tissue homeostasis is crucial for multicellular organisms, wherein the loss of cells is compensated by generating new cells with the capacity for proliferation and differentiation. At the origin of these populations are the stem cells, which have the potential to give rise to cells with both capabilities, and persevere for a long time through the self-renewal and quiescence. Since the discovery of stem cells, an enormous effort has been focused on learning about their functions and the molecular regulation behind them. Wnt signaling is widely recognized as essential for normal and cancer stem cell. Moreover, β-catenin-dependent Wnt pathway, referred to as canonical, has gained attention, while β-catenin-independent Wnt pathways, known as non-canonical, have remained conspicuously less explored. However, recent evidence about non-canonical Wnt pathways in stem cells begins to lay the foundations of a conceivably vast field, and on which we aim to explain this in the present review. In this regard, we addressed the different aspects in which non-canonical Wnt pathways impact the properties of stem cells, both under normal conditions and also under disease, specifically in cancer. Graphical abstract

Neurotensin counteracts hair growth inhibition induced by chronic restraint stress

“…35,36 In the process of normal hair growth, Wnt proteins bind to their receptors on hair follicle cells, thereby initiating the activation of the Wnt/β-catenin pathway. 37 This activation triggers the accumulation and translocation of β-catenin into the nucleus, where it effectively regulates the expression of target genes associated with hair growth and maintenance. 38 These specific genes facilitate the proliferation of hair follicle cells, extend the anagen (growth) phase of the hair cycle and inhibit both catagen (regression) and telogen (resting) phases.…”

“…In various in vitro and in vivo studies, several plant‐derived chemicals have been reported to promote hair growth by activating Wnt/β‐catenin signalling 35,36 . In the process of normal hair growth, Wnt proteins bind to their receptors on hair follicle cells, thereby initiating the activation of the Wnt/β‐catenin pathway 37 . This activation triggers the accumulation and translocation of β‐catenin into the nucleus, where it effectively regulates the expression of target genes associated with hair growth and maintenance 38 .…”

Comprehensive insights into rheumatoid arthritis: Pathophysiology, current therapies and herbal alternatives for effective disease management

“…The non‐canonical Wnt cascade can be further divided into the Wnt/planar cell polarity pathway and the Wnt/Ca 2+ pathway. The Wnt/Ca 2+ pathway results in the discharge of intracellular calcium and promotes calcium‐dependant mechanisms, while the Wnt/planar cell polarity pathway is responsible for the development of cell polarity, cytoskeletal re‐arrangement, cell migration and adhesion (Sánchez & Flores, 2023). Instead of LRP5/6, non‐canonical Wnt ligands (namely Wnt3a, Wnt4, Wnt5a, Wnt5b, Wnt7b, Wnt10b and Wnt16) bind to different co‐receptors like TYKs and receptor TYK‐like orphan receptor (Lojk & Marc, 2021).…”