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      Regulation of Wnt/β-catenin signaling by Marek’s disease virus in vitro and in vivo

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          Abstract

          Marek’s disease virus (MDV) infection causes immunosuppression in the host, ultimately inducing tumor formation and causing significant economic losses to the poultry industry. While the abnormal activation of the Wnt/β-catenin signaling pathway is closely associated with the occurrence and development of tumors. However, the relationship between MDV and the Wnt/β-catenin pathway remains unclear. In this study, we found that the MDV RB1B strain, but not the MDV vaccine strain CVI988, activated the Wnt/β-catenin signaling pathway by increasing the phosphorylation level of GSK-3β in chicken embryo fibroblast (CEF). In vivo infection experiments in SPF chickens also confirmed that the RB1B strain activated the Wnt/β-catenin signaling pathway, while the CVI988 strain did not lead to its activation. Moreover, unlike the Meq protein encoded by the CVI988 strain, the Meq protein encoded by the RB1B strain specifically activated the Wnt/β-catenin signaling pathway in CEF cells. The findings from these studies extend our understanding of the regulation of Wnt/β-catenin signaling by MDV, which make a new contribution to understanding the virus–host interactions of MDV.

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          Most cited references26

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          Wnt/β-Catenin Signaling, Disease, and Emerging Therapeutic Modalities.

          The WNT signal transduction cascade is a main regulator of development throughout the animal kingdom. Wnts are also key drivers of most types of tissue stem cells in adult mammals. Unsurprisingly, mutated Wnt pathway components are causative to multiple growth-related pathologies and to cancer. Here, we describe the core Wnt/β-catenin signaling pathway, how it controls stem cells, and contributes to disease. Finally, we discuss strategies for Wnt-based therapies.
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            WNT signalling pathways as therapeutic targets in cancer.

            Since the initial discovery of the oncogenic activity of WNT1 in mouse mammary glands, our appreciation for the complex roles for WNT signalling pathways in cancer has increased dramatically. WNTs and their downstream effectors regulate various processes that are important for cancer progression, including tumour initiation, tumour growth, cell senescence, cell death, differentiation and metastasis. Although WNT signalling pathways have been difficult to target, improved drug-discovery platforms and new technologies have facilitated the discovery of agents that can alter WNT signalling in preclinical models, thus setting the stage for clinical trials in humans.
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              The Wnt signaling pathway in cancer.

              The Wnt signaling pathway is critically involved in both the development and homeostasis of tissues via regulation of their endogenous stem cells. Aberrant Wnt signaling has been described as a key player in the initiation of and/or maintenance and development of many cancers, via affecting the behavior of Cancer Stem Cells (CSCs). CSCs are considered by most to be responsible for establishment of the tumor and also for disease relapse, as they possess inherent drug-resistance properties. The development of new therapeutic compounds targeting the Wnt signaling pathway promises new hope to eliminate CSCs and achieve cancer eradication. However, a major challenge resides in developing a strategy efficient enough to target the dysregulated Wnt pathway in CSCs, while being safe enough to not damage the normal somatic stem cell population required for tissue homeostasis and repair. Here we review recent therapeutic approaches to target the Wnt pathway and their clinical applications.
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                Author and article information

                Contributors
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                URI : https://loop.frontiersin.org/people/1190311/overviewRole:
                URI : https://loop.frontiersin.org/people/105126/overviewRole: Role:
                URI : https://loop.frontiersin.org/people/850454/overviewRole: Role:
                URI : https://loop.frontiersin.org/people/762417/overviewRole: Role: Role: Role: Role: Role: Role:
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                03 April 2024
                2024
                : 15
                : 1388862
                Affiliations
                [1] 1Ministry of Education Key Laboratory for Avian Preventive Medicine, Yangzhou University , Yangzhou, China
                [2] 2Jiangsu Key Laboratory of Preventive Veterinary Medicine, Yangzhou University , Yangzhou, China
                [3] 3Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University , Yangzhou, Jiangsu, China
                [4] 4The Pirbright Institute & UK-China Centre of Excellence for Research on Avian Diseases , Surrey, United Kingdom
                Author notes

                Edited by: Chengming Wang, Auburn University, United States

                Reviewed by: Lanjing Wei, University of Kansas, United States

                Defang Zhou, Shandong Agricultural University, China

                *Correspondence: Kun Qian, qiankun@ 123456yzu.edu.cn
                Article
                10.3389/fmicb.2024.1388862
                11025357
                38638910
                f1aed30c-d7ad-4f5a-b7be-12cb44a41afd
                Copyright © 2024 Xu, Xu, He, Shao, Yao, Qin and Qian.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 20 February 2024
                : 20 March 2024
                Page count
                Figures: 7, Tables: 1, Equations: 0, References: 26, Pages: 10, Words: 5500
                Funding
                The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This research was supported by the National Key Research and Development Program (grant no. 2023YFE0106100), the National Natural Science Foundation of China (grant no. 32072839 and 32272970), Biotechnology and Biological Sciences Research Council (BBSRC) grants BB/R012865/1 and BBS/OS/NW/000007, Foundation of Cultivate Middle-aged and Yong Science Leasers of Colleges and Universities of Jiangsu Province, Discipline Innovation and Intellectual Introduction Program for universities (111 Project D18007), the Priority Academic Program Development of Jiangsu Higher Education Institutions and the Jiangsu Co-innovation Centre for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses.
                Categories
                Microbiology
                Original Research
                Custom metadata
                Virology

                Microbiology & Virology
                marek’s disease virus,wnt/β-catenin signaling pathway,rb1b,cvi988,meq
                Microbiology & Virology
                marek’s disease virus, wnt/β-catenin signaling pathway, rb1b, cvi988, meq

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