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The evolving roles of wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

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Genes & Diseases 2024年第3期11卷 155-187页

作者： Michael Yu Kevin Qin Jiaming Fan Guozhi Zhao Piao Zhao Wei Zeng Connie Chen Annie Wang Yonghui Wang jiamin Zhong Yi Zhu William Wagstaff Rex C.Haydon Hue H.Luu Sherwin Ho Michael J.Lee Jason Strelzow Russell R.Reid Tong-Chuan He School of Medicine Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of Orthopedic Surgery The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Department of Orthopaedic Surgery Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Department of Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China

The evolutionarily conserved wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across species.wnt proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)wnt signaling pathways.Cellular behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known wnt signaling paths.wnt signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various tissues.This includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem cells.wnt signaling has also been implicated in tumor cells that exhibit stem cell-like properties.wnt signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone disorders.Not surprisingly,aberrant wnt signaling is also associated with a wide variety of diseases,including cancer.Mutations of wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and metastasis.Altogether,advances in the understand-ing of dysregulated wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the wnt pathway.Beginning with a brief overview of the mechanisms of canonical and non-canonical wnt,this review aims to summarize the cur-rent knowledge of wnt signaling in stem cells,aberrations to the wnt pathway associated with diseases,and novel therapeutics targeting the wnt pathway in preclinical and clinical studies.

关键词： β-Catenin Cancer canonical wnt Disease non-canonical wnt Stem cells Targeted therapy wnt signaling

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