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      Activating transcription factor 5 (ATF5) promotes tumorigenic capability and activates the Wnt/b-catenin pathway in bladder cancer

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          Abstract

          Background

          In bladder cancer, up to 70% of patients will relapse after resection within 5 years, in which the mechanism underlying the recurrence remains largely unclear.

          Methods

          Quantitative real-time PCR, western blot and immunohistochemistry were conducted. The assays of tumor sphere formation and tumor xenograft were further performed to assess the potential biological roles of ATF5 (activating transcription factor 5). Chromatin immunoprecipitation-qPCR and luciferase activity assays were carried out to explore the potential molecular mechanism. A two-tailed paired Student's t-test, χ 2 test, Kaplan Meier and Cox regression analyses, and Spearman's rank correlation coefficients were used for statistical analyses.

          Results

          ATF5 is elevated in bladder urothelial cancer (BLCA) tissues, especially in recurrent BLCA, which confers a poor prognosis. Overexpressing ATF5 significantly enhanced, whereas silencing ATF5 inhibited, the capability of tumor sphere formation in bladder cancer cells. Mechanically, ATF5 could directly bind to and stimulate the promoter of DVL1 gene, resulting in activation of Wnt/β-catenin pathway.

          Conclusions

          This study provides a novel insight into a portion of the mechanism underlying high recurrence potential of BLCA, presenting ATF5 as a prognostic factor or potential therapeutic target for preventing recurrence in BLCA.

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          Most cited references40

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          Induction of pluripotent stem cells from adult human fibroblasts by defined factors.

          Successful reprogramming of differentiated human somatic cells into a pluripotent state would allow creation of patient- and disease-specific stem cells. We previously reported generation of induced pluripotent stem (iPS) cells, capable of germline transmission, from mouse somatic cells by transduction of four defined transcription factors. Here, we demonstrate the generation of iPS cells from adult human dermal fibroblasts with the same four factors: Oct3/4, Sox2, Klf4, and c-Myc. Human iPS cells were similar to human embryonic stem (ES) cells in morphology, proliferation, surface antigens, gene expression, epigenetic status of pluripotent cell-specific genes, and telomerase activity. Furthermore, these cells could differentiate into cell types of the three germ layers in vitro and in teratomas. These findings demonstrate that iPS cells can be generated from adult human fibroblasts.
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            Wnt/β-catenin signaling and disease.

            The WNT signal transduction cascade controls myriad biological phenomena throughout development and adult life of all animals. In parallel, aberrant Wnt signaling underlies a wide range of pathologies in humans. In this Review, we provide an update of the core Wnt/β-catenin signaling pathway, discuss how its various components contribute to disease, and pose outstanding questions to be addressed in the future. Copyright © 2012 Elsevier Inc. All rights reserved.
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              Cancer stem cells revisited.

              The cancer stem cell (CSC) concept was proposed four decades ago, and states that tumor growth, analogous to the renewal of healthy tissues, is fueled by small numbers of dedicated stem cells. It has gradually become clear that many tumors harbor CSCs in dedicated niches, and yet their identification and eradication has not been as obvious as was initially hoped. Recently developed lineage-tracing and cell-ablation strategies have provided insights into CSC plasticity, quiescence, renewal, and therapeutic response. Here we discuss new developments in the CSC field in relationship to changing insights into how normal stem cells maintain healthy tissues. Expectations in the field have become more realistic, and now, the first successes of therapies based on the CSC concept are emerging.
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                Author and article information

                Contributors
                zhuting90@foxmail.com
                cundongliu@163.com
                Journal
                Cancer Cell Int
                Cancer Cell Int
                Cancer Cell International
                BioMed Central (London )
                1475-2867
                11 December 2021
                11 December 2021
                2021
                : 21
                : 660
                Affiliations
                [1 ]GRID grid.413107.0, Department of Urology, , The Third Affiliated Hospital of Southern Medical University, ; Guangzhou, 510630 Guangdong People’s Republic of China
                [2 ]GRID grid.502971.8, ISNI 0000 0004 1758 1569, Department of Urology, , The First People’s Hospital of Zhaoqing, ; Zhaoqing, 526020 China
                [3 ]GRID grid.410737.6, ISNI 0000 0000 8653 1072, Department of Laboratory Medicine, , Affiliated Cancer Hospital & Institute of Guangzhou Medical University, ; Guangzhou, 510095 Guangdong People’s Republic of China
                Author information
                http://orcid.org/0000-0002-2098-1139
                Article
                2315
                10.1186/s12935-021-02315-x
                8665506
                34895217
                ebfa0a4b-8e0e-445b-a1fb-2e7e977f3471
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 7 September 2021
                : 1 November 2021
                Funding
                Funded by: Guangzhou Science and Technology Planning Project
                Award ID: 202102021056
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81902991
                Award Recipient :
                Funded by: Youth Project of The Third Affiliated Hospital of Southern Medical University
                Award ID: QD2019N010
                Award Recipient :
                Categories
                Primary Research
                Custom metadata
                © The Author(s) 2021

                Oncology & Radiotherapy
                atf5,tumorigenicity,recurrence,wnt/β-catenin signaling,bladder cancer
                Oncology & Radiotherapy
                atf5, tumorigenicity, recurrence, wnt/β-catenin signaling, bladder cancer

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