The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities
作者全名：Yu, Michael; Qin, Kevin; Fan, Jiaming; Zhao, Guozhi; Zhao, Piao; Zeng, Wei; Chen, Connie; Wang, Annie; Wang, Yonghui; Zhong, Jiamin; Zhu, Yi; Wagstaff, William; Haydon, Rex C.; Luu, Hue H.; Ho, Sherwin; Lee, Michael J.; Strelzow, Jason; Reid, Russell R.; He, Tong-Chuan
作者地址：[Yu, Michael; Qin, Kevin] Rosalind Franklin Univ Med & Sci, Sch Med, N Chicago, IL 60064 USA; [Yu, Michael; Qin, Kevin; Fan, Jiaming; Zhao, Guozhi; Zhao, Piao; Zeng, Wei; Chen, Connie; Wang, Annie; Wang, Yonghui; Zhong, Jiamin; Zhu, Yi; Wagstaff, William; Haydon, Rex C.; Luu, Hue H.; Ho, Sherwin; Lee, Michael J.; Strelzow, Jason; Reid, Russell R.; He, Tong-Chuan] Univ Chicago Med Ctr, Dept Orthoped Surg & Rehabil Med, Mol Oncol Lab, Chicago, IL 60637 USA; [Fan, Jiaming; Zhong, Jiamin] Chongqing Med Univ, Sch Lab Med, Minist Educ Key Lab Diagnost Med, Chongqing 400016, Peoples R China; [Fan, Jiaming; Zhong, Jiamin] Chongqing Med Univ, Sch Lab Med, Dept Clin Biochem, Chongqing 400016, Peoples R China; [Zhao, Guozhi; Zhao, Piao] Chongqing Med Univ, Affiliated Hosp 1, Dept Orthoped Surg, Chongqing 400016, Peoples R China; [Zhao, Guozhi; Zhao, Piao] Chongqing Med Univ, Affiliated Hosp 1, Dept Urol, Chongqing 400016, Peoples R China; [Wang, Yonghui] Shanghai Jiao Tong Univ, Sch Med, Dept Clin Lab Med, Shanghai 200000, Peoples R China; [Zhu, Yi] Chinese Acad Med Sci & Peking Union Med Coll, Dept Orthopaed Surg, Beijing 100730, Peoples R China; [Reid, Russell R.; He, Tong-Chuan] Univ Chicago Med Ctr, Dept Surg Sect Plast Surg, Lab Craniofacial Suture Biol & Dev, Chicago, IL 60637 USA; [Zeng, Wei] Guangdong Med Univ, Dongguan Affiliated Hosp 1, Dept Neurol, Dongguan 523475, Guangdong, Peoples R China; [He, Tong-Chuan] Univ Chicago Med Ctr, Mol Oncol Lab, 5841 South Maryland Ave,MC3079, Chicago, IL 60637 USA; [Reid, Russell R.] Univ Chicago Med Ctr, Dept Surg Sect Plast Surg, Lab Craniofacial Suture Biol & Dev, 5841 S Maryland Ave,Rm J-641,MC 6035, Chicago, IL 60637 USA
通信作者：He, TC (通讯作者)，Univ Chicago Med Ctr, Mol Oncol Lab, 5841 South Maryland Ave,MC3079, Chicago, IL 60637 USA.; Reid, RR (通讯作者)，Univ Chicago Med Ctr, Dept Surg Sect Plast Surg, Lab Craniofacial Suture Biol & Dev, 5841 S Maryland Ave,Rm J-641,MC 6035, Chicago, IL 60637 USA.
来源：GENES & DISEASES
ESI学科分类：MOLECULAR BIOLOGY & GENETICS
WOS号：WOS:001214152300001
JCR分区：Q1
影响因子：6.9
年份：2024
卷号：11
期号：3
开始页：
结束页：
文献类型：Article
关键词：13-Catenin; Cancer; Canonical Wnt; Disease; Non-canonical Wnt; Stem cells; Targeted therapy; Wnt signaling
摘要：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 (13-catenin dependent) and non-canonical (13-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, epithelialemesenchymal 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. (c) 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).
基金机构：National Institutes of Health [CA226303, DE030480]; Natural Science Foundation of China [82102696]; Science and Technology Research Plan Project of Chongqing Education Commission(China) [KJQN201900410]; University of Chicago Cancer Center Support Grant [P30CA014599]; Funding for Postdoctoral Research (Chongqing Human Resources and Social Security Bureau, Chongqing, China); National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health [5UL1TR002389]; Mabel Green Myers Research Endowment Fund; University of Chicago Orthopaedics Alumni Fund
基金资助正文：The reported work was supported in part by research grants from the National Institutes of Health (No. CA226303 to TCH and No. DE030480 to RRR). JF was supported in part by research grants from the Natural Science Foundation of China (No. 82102696), the 2019 Science and Technology Research Plan Project of Chongqing Education Commission(China) (No. KJQN201900410), and the 2019 Funding for Postdoctoral Research (Chongqing Human Resources and Social Security Bureau No. 298, Chongqing, China). WW was supported by the Medical Scientist Training Program of the National Institutes of Health (No. T32 GM007281). This project was also supported in part by The University of Chicago Cancer Center Support Grant (No. P30CA014599) and the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (No.5UL1TR002389). TCH was also supported by the Mabel Green Myers Research Endowment Fund and The University of Chicago Orthopaedics Alumni Fund. Funding sources were not involved in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
