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Cell survival, DNA damage, and oncogenic transformation after a transient and reversible apoptotic response
Apoptosis serves as a protective mechanism by eliminating damaged cells through programmed cell death. After apoptotic cells pass critical checkpoints, including mitochondrial fragmentation, executioner caspase activation, and DNA damage, it is assumed that cell death inevitably follows. However, th...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374744/ https://www.ncbi.nlm.nih.gov/pubmed/22535522 http://dx.doi.org/10.1091/mbc.E11-11-0926 |
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author | Tang, Ho Lam Tang, Ho Man Mak, Keng Hou Hu, Shaomin Wang, Shan Shan Wong, Kit Man Wong, Chung Sing Timothy Wu, Hoi Yan Law, Hiu Tung Liu, Kan Talbot, C. Conover Lau, Wan Keung Montell, Denise J. Fung, Ming Chiu |
author_facet | Tang, Ho Lam Tang, Ho Man Mak, Keng Hou Hu, Shaomin Wang, Shan Shan Wong, Kit Man Wong, Chung Sing Timothy Wu, Hoi Yan Law, Hiu Tung Liu, Kan Talbot, C. Conover Lau, Wan Keung Montell, Denise J. Fung, Ming Chiu |
author_sort | Tang, Ho Lam |
collection | PubMed |
description | Apoptosis serves as a protective mechanism by eliminating damaged cells through programmed cell death. After apoptotic cells pass critical checkpoints, including mitochondrial fragmentation, executioner caspase activation, and DNA damage, it is assumed that cell death inevitably follows. However, this assumption has not been tested directly. Here we report an unexpected reversal of late-stage apoptosis in primary liver and heart cells, macrophages, NIH 3T3 fibroblasts, cervical cancer HeLa cells, and brain cells. After exposure to an inducer of apoptosis, cells exhibited multiple morphological and biochemical hallmarks of late-stage apoptosis, including mitochondrial fragmentation, caspase-3 activation, and DNA damage. Surprisingly, the vast majority of dying cells arrested the apoptotic process and recovered when the inducer was washed away. Of importance, some cells acquired permanent genetic changes and underwent oncogenic transformation at a higher frequency than controls. Global gene expression analysis identified a molecular signature of the reversal process. We propose that reversal of apoptosis is an unanticipated mechanism to rescue cells from crisis and propose to name this mechanism “anastasis” (Greek for “rising to life”). Whereas carcinogenesis represents a harmful side effect, potential benefits of anastasis could include preservation of cells that are difficult to replace and stress-induced genetic diversity. |
format | Online Article Text |
id | pubmed-3374744 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-33747442012-08-30 Cell survival, DNA damage, and oncogenic transformation after a transient and reversible apoptotic response Tang, Ho Lam Tang, Ho Man Mak, Keng Hou Hu, Shaomin Wang, Shan Shan Wong, Kit Man Wong, Chung Sing Timothy Wu, Hoi Yan Law, Hiu Tung Liu, Kan Talbot, C. Conover Lau, Wan Keung Montell, Denise J. Fung, Ming Chiu Mol Biol Cell Articles Apoptosis serves as a protective mechanism by eliminating damaged cells through programmed cell death. After apoptotic cells pass critical checkpoints, including mitochondrial fragmentation, executioner caspase activation, and DNA damage, it is assumed that cell death inevitably follows. However, this assumption has not been tested directly. Here we report an unexpected reversal of late-stage apoptosis in primary liver and heart cells, macrophages, NIH 3T3 fibroblasts, cervical cancer HeLa cells, and brain cells. After exposure to an inducer of apoptosis, cells exhibited multiple morphological and biochemical hallmarks of late-stage apoptosis, including mitochondrial fragmentation, caspase-3 activation, and DNA damage. Surprisingly, the vast majority of dying cells arrested the apoptotic process and recovered when the inducer was washed away. Of importance, some cells acquired permanent genetic changes and underwent oncogenic transformation at a higher frequency than controls. Global gene expression analysis identified a molecular signature of the reversal process. We propose that reversal of apoptosis is an unanticipated mechanism to rescue cells from crisis and propose to name this mechanism “anastasis” (Greek for “rising to life”). Whereas carcinogenesis represents a harmful side effect, potential benefits of anastasis could include preservation of cells that are difficult to replace and stress-induced genetic diversity. The American Society for Cell Biology 2012-06-15 /pmc/articles/PMC3374744/ /pubmed/22535522 http://dx.doi.org/10.1091/mbc.E11-11-0926 Text en © 2012 Tang et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Tang, Ho Lam Tang, Ho Man Mak, Keng Hou Hu, Shaomin Wang, Shan Shan Wong, Kit Man Wong, Chung Sing Timothy Wu, Hoi Yan Law, Hiu Tung Liu, Kan Talbot, C. Conover Lau, Wan Keung Montell, Denise J. Fung, Ming Chiu Cell survival, DNA damage, and oncogenic transformation after a transient and reversible apoptotic response |
title | Cell survival, DNA damage, and oncogenic transformation after a transient and reversible apoptotic response |
title_full | Cell survival, DNA damage, and oncogenic transformation after a transient and reversible apoptotic response |
title_fullStr | Cell survival, DNA damage, and oncogenic transformation after a transient and reversible apoptotic response |
title_full_unstemmed | Cell survival, DNA damage, and oncogenic transformation after a transient and reversible apoptotic response |
title_short | Cell survival, DNA damage, and oncogenic transformation after a transient and reversible apoptotic response |
title_sort | cell survival, dna damage, and oncogenic transformation after a transient and reversible apoptotic response |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374744/ https://www.ncbi.nlm.nih.gov/pubmed/22535522 http://dx.doi.org/10.1091/mbc.E11-11-0926 |
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