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Apoptosis-induced nuclear expulsion in tumor cells drives S100a4-mediated metastatic outgrowth through the RAGE pathway
Most tumor cells undergo apoptosis in circulation and at the metastatic organ sites due to host immune surveillance and a hostile microenvironment. It remains to be elucidated whether dying tumor cells have a direct effect on live tumor cells during the metastatic process and what the underlying mec...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10042736/ https://www.ncbi.nlm.nih.gov/pubmed/36973439 http://dx.doi.org/10.1038/s43018-023-00524-z |
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author | Park, Woo-Yong Gray, Justin M. Holewinski, Ronald J. Andresson, Thorkell So, Jae Young Carmona-Rivera, Carmelo Hollander, M. Christine Yang, Howard H. Lee, Maxwell Kaplan, Mariana J. Cappell, Steven D. Yang, Li |
author_facet | Park, Woo-Yong Gray, Justin M. Holewinski, Ronald J. Andresson, Thorkell So, Jae Young Carmona-Rivera, Carmelo Hollander, M. Christine Yang, Howard H. Lee, Maxwell Kaplan, Mariana J. Cappell, Steven D. Yang, Li |
author_sort | Park, Woo-Yong |
collection | PubMed |
description | Most tumor cells undergo apoptosis in circulation and at the metastatic organ sites due to host immune surveillance and a hostile microenvironment. It remains to be elucidated whether dying tumor cells have a direct effect on live tumor cells during the metastatic process and what the underlying mechanisms are. Here we report that apoptotic cancer cells enhance the metastatic outgrowth of surviving cells through Padi4-mediated nuclear expulsion. Tumor cell nuclear expulsion results in an extracellular DNA–protein complex that is enriched with receptor for advanced glycation endproducts (RAGE) ligands. The chromatin-bound RAGE ligand S100a4 activates RAGE receptors in neighboring surviving tumor cells, leading to Erk activation. In addition, we identified nuclear expulsion products in human patients with breast, bladder and lung cancer and a nuclear expulsion signature correlated with poor prognosis. Collectively, our study demonstrates how apoptotic cell death can enhance the metastatic outgrowth of neighboring live tumor cells. |
format | Online Article Text |
id | pubmed-10042736 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-100427362023-03-29 Apoptosis-induced nuclear expulsion in tumor cells drives S100a4-mediated metastatic outgrowth through the RAGE pathway Park, Woo-Yong Gray, Justin M. Holewinski, Ronald J. Andresson, Thorkell So, Jae Young Carmona-Rivera, Carmelo Hollander, M. Christine Yang, Howard H. Lee, Maxwell Kaplan, Mariana J. Cappell, Steven D. Yang, Li Nat Cancer Article Most tumor cells undergo apoptosis in circulation and at the metastatic organ sites due to host immune surveillance and a hostile microenvironment. It remains to be elucidated whether dying tumor cells have a direct effect on live tumor cells during the metastatic process and what the underlying mechanisms are. Here we report that apoptotic cancer cells enhance the metastatic outgrowth of surviving cells through Padi4-mediated nuclear expulsion. Tumor cell nuclear expulsion results in an extracellular DNA–protein complex that is enriched with receptor for advanced glycation endproducts (RAGE) ligands. The chromatin-bound RAGE ligand S100a4 activates RAGE receptors in neighboring surviving tumor cells, leading to Erk activation. In addition, we identified nuclear expulsion products in human patients with breast, bladder and lung cancer and a nuclear expulsion signature correlated with poor prognosis. Collectively, our study demonstrates how apoptotic cell death can enhance the metastatic outgrowth of neighboring live tumor cells. Nature Publishing Group US 2023-03-27 2023 /pmc/articles/PMC10042736/ /pubmed/36973439 http://dx.doi.org/10.1038/s43018-023-00524-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Park, Woo-Yong Gray, Justin M. Holewinski, Ronald J. Andresson, Thorkell So, Jae Young Carmona-Rivera, Carmelo Hollander, M. Christine Yang, Howard H. Lee, Maxwell Kaplan, Mariana J. Cappell, Steven D. Yang, Li Apoptosis-induced nuclear expulsion in tumor cells drives S100a4-mediated metastatic outgrowth through the RAGE pathway |
title | Apoptosis-induced nuclear expulsion in tumor cells drives S100a4-mediated metastatic outgrowth through the RAGE pathway |
title_full | Apoptosis-induced nuclear expulsion in tumor cells drives S100a4-mediated metastatic outgrowth through the RAGE pathway |
title_fullStr | Apoptosis-induced nuclear expulsion in tumor cells drives S100a4-mediated metastatic outgrowth through the RAGE pathway |
title_full_unstemmed | Apoptosis-induced nuclear expulsion in tumor cells drives S100a4-mediated metastatic outgrowth through the RAGE pathway |
title_short | Apoptosis-induced nuclear expulsion in tumor cells drives S100a4-mediated metastatic outgrowth through the RAGE pathway |
title_sort | apoptosis-induced nuclear expulsion in tumor cells drives s100a4-mediated metastatic outgrowth through the rage pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10042736/ https://www.ncbi.nlm.nih.gov/pubmed/36973439 http://dx.doi.org/10.1038/s43018-023-00524-z |
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