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Human Cancer Cells Signal Their Competitive Fitness Through MYC Activity
MYC-mediated cell competition is a cell-cell interaction mechanism known to play an evolutionary role during development from Drosophila to mammals. Cells expressing low levels of MYC, called losers, are committed to die by nearby cells with high MYC activity, called winners, that overproliferate to...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5626713/ https://www.ncbi.nlm.nih.gov/pubmed/28974715 http://dx.doi.org/10.1038/s41598-017-13002-1 |
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author | Di Giacomo, Simone Sollazzo, Manuela de Biase, Dario Ragazzi, Moira Bellosta, Paola Pession, Annalisa Grifoni, Daniela |
author_facet | Di Giacomo, Simone Sollazzo, Manuela de Biase, Dario Ragazzi, Moira Bellosta, Paola Pession, Annalisa Grifoni, Daniela |
author_sort | Di Giacomo, Simone |
collection | PubMed |
description | MYC-mediated cell competition is a cell-cell interaction mechanism known to play an evolutionary role during development from Drosophila to mammals. Cells expressing low levels of MYC, called losers, are committed to die by nearby cells with high MYC activity, called winners, that overproliferate to compensate for cell loss, so that the fittest cells be selected for organ formation. Given MYC’s consolidated role in oncogenesis, cell competition is supposed to be relevant to cancer, but its significance in human malignant contexts is largely uncharacterised. Here we show stereotypical patterns of MYC-mediated cell competition in human cancers: MYC-upregulating cells and apoptotic cells were indeed repeatedly found at the tumour-stroma interface and within the tumour parenchyma. Cell death amount in the stromal compartment and MYC protein level in the tumour were highly correlated regardless of tumour type and stage. Moreover, we show that MYC modulation in heterotypic co-cultures of human cancer cells is sufficient as to subvert their competitive state, regardless of genetic heterogeneity. Altogether, our findings suggest that the innate role of MYC-mediated cell competition in development is conserved in human cancer, with malignant cells using MYC activity to colonise the organ at the expense of less performant neighbours. |
format | Online Article Text |
id | pubmed-5626713 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-56267132017-10-12 Human Cancer Cells Signal Their Competitive Fitness Through MYC Activity Di Giacomo, Simone Sollazzo, Manuela de Biase, Dario Ragazzi, Moira Bellosta, Paola Pession, Annalisa Grifoni, Daniela Sci Rep Article MYC-mediated cell competition is a cell-cell interaction mechanism known to play an evolutionary role during development from Drosophila to mammals. Cells expressing low levels of MYC, called losers, are committed to die by nearby cells with high MYC activity, called winners, that overproliferate to compensate for cell loss, so that the fittest cells be selected for organ formation. Given MYC’s consolidated role in oncogenesis, cell competition is supposed to be relevant to cancer, but its significance in human malignant contexts is largely uncharacterised. Here we show stereotypical patterns of MYC-mediated cell competition in human cancers: MYC-upregulating cells and apoptotic cells were indeed repeatedly found at the tumour-stroma interface and within the tumour parenchyma. Cell death amount in the stromal compartment and MYC protein level in the tumour were highly correlated regardless of tumour type and stage. Moreover, we show that MYC modulation in heterotypic co-cultures of human cancer cells is sufficient as to subvert their competitive state, regardless of genetic heterogeneity. Altogether, our findings suggest that the innate role of MYC-mediated cell competition in development is conserved in human cancer, with malignant cells using MYC activity to colonise the organ at the expense of less performant neighbours. Nature Publishing Group UK 2017-10-03 /pmc/articles/PMC5626713/ /pubmed/28974715 http://dx.doi.org/10.1038/s41598-017-13002-1 Text en © The Author(s) 2017 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 Di Giacomo, Simone Sollazzo, Manuela de Biase, Dario Ragazzi, Moira Bellosta, Paola Pession, Annalisa Grifoni, Daniela Human Cancer Cells Signal Their Competitive Fitness Through MYC Activity |
title | Human Cancer Cells Signal Their Competitive Fitness Through MYC Activity |
title_full | Human Cancer Cells Signal Their Competitive Fitness Through MYC Activity |
title_fullStr | Human Cancer Cells Signal Their Competitive Fitness Through MYC Activity |
title_full_unstemmed | Human Cancer Cells Signal Their Competitive Fitness Through MYC Activity |
title_short | Human Cancer Cells Signal Their Competitive Fitness Through MYC Activity |
title_sort | human cancer cells signal their competitive fitness through myc activity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5626713/ https://www.ncbi.nlm.nih.gov/pubmed/28974715 http://dx.doi.org/10.1038/s41598-017-13002-1 |
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