Wnt/β-catenin signalling: function, biological mechanisms, and therapeutic opportunities

Wnt/β-catenin signalling: function, biological mechanisms, and therapeutic opportunities

2022 | Jiaqi Liu, Qing Xiao, Jian Xiao, Chenxi Niu, Yuanyuan Li, Xiaojun Zhang, Zhengwei Zhou, Guang Shu and Gang Yin
The Wnt/β-catenin pathway is a critical signaling pathway involved in embryonic development and adult tissue homeostasis. Dysregulation of this pathway is associated with various diseases, including cancer and non-cancer conditions. This review article provides a comprehensive overview of the Wnt/β-catenin pathway, its components, and its role in disease. The pathway consists of extracellular, membrane, cytoplasmic, and nuclear segments. Extracellular signals are mediated by Wnt proteins, while membrane receptors include Frizzled and LRP5/6. The cytoplasmic segment includes β-catenin, DVL, GSK-3β, AXIN, APC, and CK1. The nuclear segment involves β-catenin, TCF/LEF, and downstream target genes. The canonical Wnt pathway is activated by Wnt ligands binding to membrane receptors, leading to β-catenin stabilization and nuclear translocation, which activates target genes involved in cell proliferation, survival, differentiation, and migration. The noncanonical Wnt pathways regulate cell polarity and migration. The Wnt/β-catenin pathway plays a crucial role in tissue renewal, such as in the small-intestinal epithelium, liver metabolism, lung tissue repair, hair follicle renewal, and bone development. The pathway is regulated by various molecules, including sFRPs, WIF, glypicans, Tiki, and Notum, which inhibit Wnt signaling. Other regulators, such as R-spondins, Norrin, and DKKs, can activate or inhibit the pathway. Non-coding RNAs, including miRNAs and lncRNAs, also regulate the Wnt/β-catenin pathway. The pathway is involved in various diseases, including lung diseases, cardiovascular diseases, bone diseases, and neurodegenerative diseases. The Wnt/β-catenin pathway is a promising target for therapeutic interventions in disease treatment.The Wnt/β-catenin pathway is a critical signaling pathway involved in embryonic development and adult tissue homeostasis. Dysregulation of this pathway is associated with various diseases, including cancer and non-cancer conditions. This review article provides a comprehensive overview of the Wnt/β-catenin pathway, its components, and its role in disease. The pathway consists of extracellular, membrane, cytoplasmic, and nuclear segments. Extracellular signals are mediated by Wnt proteins, while membrane receptors include Frizzled and LRP5/6. The cytoplasmic segment includes β-catenin, DVL, GSK-3β, AXIN, APC, and CK1. The nuclear segment involves β-catenin, TCF/LEF, and downstream target genes. The canonical Wnt pathway is activated by Wnt ligands binding to membrane receptors, leading to β-catenin stabilization and nuclear translocation, which activates target genes involved in cell proliferation, survival, differentiation, and migration. The noncanonical Wnt pathways regulate cell polarity and migration. The Wnt/β-catenin pathway plays a crucial role in tissue renewal, such as in the small-intestinal epithelium, liver metabolism, lung tissue repair, hair follicle renewal, and bone development. The pathway is regulated by various molecules, including sFRPs, WIF, glypicans, Tiki, and Notum, which inhibit Wnt signaling. Other regulators, such as R-spondins, Norrin, and DKKs, can activate or inhibit the pathway. Non-coding RNAs, including miRNAs and lncRNAs, also regulate the Wnt/β-catenin pathway. The pathway is involved in various diseases, including lung diseases, cardiovascular diseases, bone diseases, and neurodegenerative diseases. The Wnt/β-catenin pathway is a promising target for therapeutic interventions in disease treatment.
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