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AMPKα2 knockout enhances tumour inflammation through exacerbated liver injury and energy deprivation‐associated AMPKα1 activation
Tissue damage and its associated‐inflammation act as tumour initiators or propagators. AMP‐activated protein kinase (AMPK) is activated by environmental or nutritional stress factors, such as hypoxia, glucose deprivation, and other cell injury factors, to regulate cell energy balance and differentia...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378193/ https://www.ncbi.nlm.nih.gov/pubmed/30636376 http://dx.doi.org/10.1111/jcmm.13978 |
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author | Qiu, Shulan Liu, Taoyan Piao, Chunmei Wang, Ying Wang, Kefang Zhou, Yandong Cai, Lun Zheng, Shuai Lan, Feng Du, Jie |
author_facet | Qiu, Shulan Liu, Taoyan Piao, Chunmei Wang, Ying Wang, Kefang Zhou, Yandong Cai, Lun Zheng, Shuai Lan, Feng Du, Jie |
author_sort | Qiu, Shulan |
collection | PubMed |
description | Tissue damage and its associated‐inflammation act as tumour initiators or propagators. AMP‐activated protein kinase (AMPK) is activated by environmental or nutritional stress factors, such as hypoxia, glucose deprivation, and other cell injury factors, to regulate cell energy balance and differentiation. We previously have reported that AMPKα2 deficiency resulted in the energy deprivation in tumour‐bearing liver and the enhanced‐hepatocyte death. In this study, AMPKα2 knockout mice and the liver metastasis model of colon cancer cells were used to address the role of AMPKα isoforms in tumour inflammation. First, we found that the AMPKα2 deficiency exacerbated the liver injury and recruitment of macrophages. Meanwhile, although compensatory expression of AMPKα1 was not significant after AMPKα2 knockout, AMPKα1 phosphorylation was elevated in remnant liver in AMPKα2 knockout mice, which was positively associated with the enhanced energy deprivation in the AMPKα2 deficient mice. Furthermore, the activated AMPKα1 in macrophage contributed to its polarizing to tumour‐associated phenotype. Thus, the enhanced tumour‐associated inflammation and activation of AMPKα1 in the AMPKα2 deficient mice may exacerbate the tumour development by affecting the tumour inflammatory microenvironment. Our study suggests that the two isoforms of AMPKα, AMPKα1 and AMPKα2 play different roles in controlling tumour development. |
format | Online Article Text |
id | pubmed-6378193 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63781932019-03-01 AMPKα2 knockout enhances tumour inflammation through exacerbated liver injury and energy deprivation‐associated AMPKα1 activation Qiu, Shulan Liu, Taoyan Piao, Chunmei Wang, Ying Wang, Kefang Zhou, Yandong Cai, Lun Zheng, Shuai Lan, Feng Du, Jie J Cell Mol Med Original Articles Tissue damage and its associated‐inflammation act as tumour initiators or propagators. AMP‐activated protein kinase (AMPK) is activated by environmental or nutritional stress factors, such as hypoxia, glucose deprivation, and other cell injury factors, to regulate cell energy balance and differentiation. We previously have reported that AMPKα2 deficiency resulted in the energy deprivation in tumour‐bearing liver and the enhanced‐hepatocyte death. In this study, AMPKα2 knockout mice and the liver metastasis model of colon cancer cells were used to address the role of AMPKα isoforms in tumour inflammation. First, we found that the AMPKα2 deficiency exacerbated the liver injury and recruitment of macrophages. Meanwhile, although compensatory expression of AMPKα1 was not significant after AMPKα2 knockout, AMPKα1 phosphorylation was elevated in remnant liver in AMPKα2 knockout mice, which was positively associated with the enhanced energy deprivation in the AMPKα2 deficient mice. Furthermore, the activated AMPKα1 in macrophage contributed to its polarizing to tumour‐associated phenotype. Thus, the enhanced tumour‐associated inflammation and activation of AMPKα1 in the AMPKα2 deficient mice may exacerbate the tumour development by affecting the tumour inflammatory microenvironment. Our study suggests that the two isoforms of AMPKα, AMPKα1 and AMPKα2 play different roles in controlling tumour development. John Wiley and Sons Inc. 2019-01-12 2019-03 /pmc/articles/PMC6378193/ /pubmed/30636376 http://dx.doi.org/10.1111/jcmm.13978 Text en © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Qiu, Shulan Liu, Taoyan Piao, Chunmei Wang, Ying Wang, Kefang Zhou, Yandong Cai, Lun Zheng, Shuai Lan, Feng Du, Jie AMPKα2 knockout enhances tumour inflammation through exacerbated liver injury and energy deprivation‐associated AMPKα1 activation |
title | AMPKα2 knockout enhances tumour inflammation through exacerbated liver injury and energy deprivation‐associated AMPKα1 activation |
title_full | AMPKα2 knockout enhances tumour inflammation through exacerbated liver injury and energy deprivation‐associated AMPKα1 activation |
title_fullStr | AMPKα2 knockout enhances tumour inflammation through exacerbated liver injury and energy deprivation‐associated AMPKα1 activation |
title_full_unstemmed | AMPKα2 knockout enhances tumour inflammation through exacerbated liver injury and energy deprivation‐associated AMPKα1 activation |
title_short | AMPKα2 knockout enhances tumour inflammation through exacerbated liver injury and energy deprivation‐associated AMPKα1 activation |
title_sort | ampkα2 knockout enhances tumour inflammation through exacerbated liver injury and energy deprivation‐associated ampkα1 activation |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378193/ https://www.ncbi.nlm.nih.gov/pubmed/30636376 http://dx.doi.org/10.1111/jcmm.13978 |
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