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Autophagy augments the self-renewal of lung cancer stem cells by the degradation of ubiquitinated p53
It has been postulated that cancer stem cells (CSCs) are involved in all aspects of human cancer, although the mechanisms governing the regulation of CSC self-renewal in the cancer state remain poorly defined. In the literature, both the pro- and anti-oncogenic activities of autophagy have been demo...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815724/ https://www.ncbi.nlm.nih.gov/pubmed/33468994 http://dx.doi.org/10.1038/s41419-021-03392-6 |
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author | Wang, Jianyu Liu, Doudou Sun, Zhiwei Ye, Ting Li, Jingyuan Zeng, Bin Zhao, Qiting Rosie Xing, H. |
author_facet | Wang, Jianyu Liu, Doudou Sun, Zhiwei Ye, Ting Li, Jingyuan Zeng, Bin Zhao, Qiting Rosie Xing, H. |
author_sort | Wang, Jianyu |
collection | PubMed |
description | It has been postulated that cancer stem cells (CSCs) are involved in all aspects of human cancer, although the mechanisms governing the regulation of CSC self-renewal in the cancer state remain poorly defined. In the literature, both the pro- and anti-oncogenic activities of autophagy have been demonstrated and are context-dependent. Mounting evidence has shown augmentation of CSC stemness by autophagy, yet mechanistic characterization and understanding are lacking. In the present study, by generating stable human lung CSC cell lines with the wild-type TP53 (A549), as well as cell lines in which TP53 was deleted (H1229), we show, for the first time, that autophagy augments the stemness of lung CSCs by degrading ubiquitinated p53. Furthermore, Zeb1 is required for TP53 regulation of CSC self-renewal. Moreover, TCGA data mining and analysis show that Atg5 and Zeb1 are poor prognostic markers of lung cancer. In summary, this study has elucidated a new CSC-based mechanism underlying the oncogenic activity of autophagy and the tumor suppressor activity of p53 in cancer, i.e., CSCs can exploit the autophagy-p53-Zeb1 axis for self-renewal, oncogenesis, and progression. |
format | Online Article Text |
id | pubmed-7815724 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-78157242021-01-28 Autophagy augments the self-renewal of lung cancer stem cells by the degradation of ubiquitinated p53 Wang, Jianyu Liu, Doudou Sun, Zhiwei Ye, Ting Li, Jingyuan Zeng, Bin Zhao, Qiting Rosie Xing, H. Cell Death Dis Article It has been postulated that cancer stem cells (CSCs) are involved in all aspects of human cancer, although the mechanisms governing the regulation of CSC self-renewal in the cancer state remain poorly defined. In the literature, both the pro- and anti-oncogenic activities of autophagy have been demonstrated and are context-dependent. Mounting evidence has shown augmentation of CSC stemness by autophagy, yet mechanistic characterization and understanding are lacking. In the present study, by generating stable human lung CSC cell lines with the wild-type TP53 (A549), as well as cell lines in which TP53 was deleted (H1229), we show, for the first time, that autophagy augments the stemness of lung CSCs by degrading ubiquitinated p53. Furthermore, Zeb1 is required for TP53 regulation of CSC self-renewal. Moreover, TCGA data mining and analysis show that Atg5 and Zeb1 are poor prognostic markers of lung cancer. In summary, this study has elucidated a new CSC-based mechanism underlying the oncogenic activity of autophagy and the tumor suppressor activity of p53 in cancer, i.e., CSCs can exploit the autophagy-p53-Zeb1 axis for self-renewal, oncogenesis, and progression. Nature Publishing Group UK 2021-01-19 /pmc/articles/PMC7815724/ /pubmed/33468994 http://dx.doi.org/10.1038/s41419-021-03392-6 Text en © The Author(s) 2021 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Wang, Jianyu Liu, Doudou Sun, Zhiwei Ye, Ting Li, Jingyuan Zeng, Bin Zhao, Qiting Rosie Xing, H. Autophagy augments the self-renewal of lung cancer stem cells by the degradation of ubiquitinated p53 |
title | Autophagy augments the self-renewal of lung cancer stem cells by the degradation of ubiquitinated p53 |
title_full | Autophagy augments the self-renewal of lung cancer stem cells by the degradation of ubiquitinated p53 |
title_fullStr | Autophagy augments the self-renewal of lung cancer stem cells by the degradation of ubiquitinated p53 |
title_full_unstemmed | Autophagy augments the self-renewal of lung cancer stem cells by the degradation of ubiquitinated p53 |
title_short | Autophagy augments the self-renewal of lung cancer stem cells by the degradation of ubiquitinated p53 |
title_sort | autophagy augments the self-renewal of lung cancer stem cells by the degradation of ubiquitinated p53 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815724/ https://www.ncbi.nlm.nih.gov/pubmed/33468994 http://dx.doi.org/10.1038/s41419-021-03392-6 |
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