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5-Azacytidine promotes invadopodia formation and tumor metastasis through the upregulation of PI3K in ovarian cancer cells
The high incidence of metastasis accounts for most of the lethality of ovarian cancer. Invadopodia are small, specialized types of machinery that degrade the extracellular matrix and are thus involved in the invasion and metastasis of cancer cells. The formation of invadopodia is regulated by both g...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5601130/ https://www.ncbi.nlm.nih.gov/pubmed/28947962 http://dx.doi.org/10.18632/oncotarget.18580 |
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author | Cao, Dan Li, Dan Huang, Yong Ma, Yu Zhang, Binglan Zhao, Chengjian Deng, Senyi Luo, Min Yin, Tao Wei, Yu-Quan Wang, Wei |
author_facet | Cao, Dan Li, Dan Huang, Yong Ma, Yu Zhang, Binglan Zhao, Chengjian Deng, Senyi Luo, Min Yin, Tao Wei, Yu-Quan Wang, Wei |
author_sort | Cao, Dan |
collection | PubMed |
description | The high incidence of metastasis accounts for most of the lethality of ovarian cancer. Invadopodia are small, specialized types of machinery that degrade the extracellular matrix and are thus involved in the invasion and metastasis of cancer cells. The formation of invadopodia is regulated by both genetic and epigenetic factors. However, the ways by which methylation/demethylation regulates the dynamics of invadopodia in ovarian cancer are largely unknown. In this study, we found that the inhibition of methylation by 5-AZ (5-Azacytidine) increased the formation of invadopodia and enhanced degradation of the extracellular matrix in ovarian cancer cells. In mouse xenograft models, treatment with 5-AZ increased the number of metastatic nodules, which suggests an elevated potential for metastasis by demethylation. Further investigation indicated that the inhibition of methylation elevated the transcription of PIK3CA and upregulated genes involved in the PI3K-AKT signaling pathway. In addition, this induction likely occurs though the epigenetic regulation of PIK3CA because analyses of the DNA methylation level of the PIK3CA promoter region found that 5-AZ treatment decreased the methylation of CpG islands in SKOV3 and A2780 cells. Our study demonstrated that epigenetic factors regulate the metastatic potential of ovarian cancer cells and provide rationale for therapies that inhibit PI3K- invadopodia-mediated metastasis. |
format | Online Article Text |
id | pubmed-5601130 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-56011302017-09-25 5-Azacytidine promotes invadopodia formation and tumor metastasis through the upregulation of PI3K in ovarian cancer cells Cao, Dan Li, Dan Huang, Yong Ma, Yu Zhang, Binglan Zhao, Chengjian Deng, Senyi Luo, Min Yin, Tao Wei, Yu-Quan Wang, Wei Oncotarget Research Paper The high incidence of metastasis accounts for most of the lethality of ovarian cancer. Invadopodia are small, specialized types of machinery that degrade the extracellular matrix and are thus involved in the invasion and metastasis of cancer cells. The formation of invadopodia is regulated by both genetic and epigenetic factors. However, the ways by which methylation/demethylation regulates the dynamics of invadopodia in ovarian cancer are largely unknown. In this study, we found that the inhibition of methylation by 5-AZ (5-Azacytidine) increased the formation of invadopodia and enhanced degradation of the extracellular matrix in ovarian cancer cells. In mouse xenograft models, treatment with 5-AZ increased the number of metastatic nodules, which suggests an elevated potential for metastasis by demethylation. Further investigation indicated that the inhibition of methylation elevated the transcription of PIK3CA and upregulated genes involved in the PI3K-AKT signaling pathway. In addition, this induction likely occurs though the epigenetic regulation of PIK3CA because analyses of the DNA methylation level of the PIK3CA promoter region found that 5-AZ treatment decreased the methylation of CpG islands in SKOV3 and A2780 cells. Our study demonstrated that epigenetic factors regulate the metastatic potential of ovarian cancer cells and provide rationale for therapies that inhibit PI3K- invadopodia-mediated metastasis. Impact Journals LLC 2017-06-20 /pmc/articles/PMC5601130/ /pubmed/28947962 http://dx.doi.org/10.18632/oncotarget.18580 Text en Copyright: © 2017 Cao et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Cao, Dan Li, Dan Huang, Yong Ma, Yu Zhang, Binglan Zhao, Chengjian Deng, Senyi Luo, Min Yin, Tao Wei, Yu-Quan Wang, Wei 5-Azacytidine promotes invadopodia formation and tumor metastasis through the upregulation of PI3K in ovarian cancer cells |
title | 5-Azacytidine promotes invadopodia formation and tumor metastasis through the upregulation of PI3K in ovarian cancer cells |
title_full | 5-Azacytidine promotes invadopodia formation and tumor metastasis through the upregulation of PI3K in ovarian cancer cells |
title_fullStr | 5-Azacytidine promotes invadopodia formation and tumor metastasis through the upregulation of PI3K in ovarian cancer cells |
title_full_unstemmed | 5-Azacytidine promotes invadopodia formation and tumor metastasis through the upregulation of PI3K in ovarian cancer cells |
title_short | 5-Azacytidine promotes invadopodia formation and tumor metastasis through the upregulation of PI3K in ovarian cancer cells |
title_sort | 5-azacytidine promotes invadopodia formation and tumor metastasis through the upregulation of pi3k in ovarian cancer cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5601130/ https://www.ncbi.nlm.nih.gov/pubmed/28947962 http://dx.doi.org/10.18632/oncotarget.18580 |
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