Human Cancer Cells Signal Their Competitive Fitness Through MYC Activity

Abstract 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 overproli...

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Autores principales:	Simone Di Giacomo, Manuela Sollazzo, Dario de Biase, Moira Ragazzi, Paola Bellosta, Annalisa Pession, Daniela Grifoni
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/67689ddb725f42bc924694dd326ec759
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spelling	oai:doaj.org-article:67689ddb725f42bc924694dd326ec7592021-12-02T15:05:55ZHuman Cancer Cells Signal Their Competitive Fitness Through MYC Activity10.1038/s41598-017-13002-12045-2322https://doaj.org/article/67689ddb725f42bc924694dd326ec7592017-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-13002-1https://doaj.org/toc/2045-2322Abstract 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.Simone Di GiacomoManuela SollazzoDario de BiaseMoira RagazziPaola BellostaAnnalisa PessionDaniela GrifoniNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Simone Di Giacomo Manuela Sollazzo Dario de Biase Moira Ragazzi Paola Bellosta Annalisa Pession Daniela Grifoni Human Cancer Cells Signal Their Competitive Fitness Through MYC Activity
description	Abstract 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	article
author	Simone Di Giacomo Manuela Sollazzo Dario de Biase Moira Ragazzi Paola Bellosta Annalisa Pession Daniela Grifoni
author_facet	Simone Di Giacomo Manuela Sollazzo Dario de Biase Moira Ragazzi Paola Bellosta Annalisa Pession Daniela Grifoni
author_sort	Simone Di Giacomo
title	Human Cancer Cells Signal Their Competitive Fitness Through MYC Activity
title_short	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_sort	human cancer cells signal their competitive fitness through myc activity
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/67689ddb725f42bc924694dd326ec759
work_keys_str_mv	AT simonedigiacomo humancancercellssignaltheircompetitivefitnessthroughmycactivity AT manuelasollazzo humancancercellssignaltheircompetitivefitnessthroughmycactivity AT dariodebiase humancancercellssignaltheircompetitivefitnessthroughmycactivity AT moiraragazzi humancancercellssignaltheircompetitivefitnessthroughmycactivity AT paolabellosta humancancercellssignaltheircompetitivefitnessthroughmycactivity AT annalisapession humancancercellssignaltheircompetitivefitnessthroughmycactivity AT danielagrifoni humancancercellssignaltheircompetitivefitnessthroughmycactivity
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Human Cancer Cells Signal Their Competitive Fitness Through MYC Activity

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