Cell state plasticity, stem cells, EMT, and the generation of intra-tumoral heterogeneity

Abstract Cellular heterogeneity in cancer represents a significant challenge. In order to develop effective and lasting therapies, it is essential to understand the source of this heterogeneity, and its role in tumor progression and therapy resistance. Here, we consider not only genetic and epigenet...

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Autores principales:	Geoffrey M. Wahl, Benjamin T. Spike
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/657a1343dbc640d09e0f4e77d11190cc
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spelling	oai:doaj.org-article:657a1343dbc640d09e0f4e77d11190cc2021-12-02T16:19:49ZCell state plasticity, stem cells, EMT, and the generation of intra-tumoral heterogeneity10.1038/s41523-017-0012-z2374-4677https://doaj.org/article/657a1343dbc640d09e0f4e77d11190cc2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41523-017-0012-zhttps://doaj.org/toc/2374-4677Abstract Cellular heterogeneity in cancer represents a significant challenge. In order to develop effective and lasting therapies, it is essential to understand the source of this heterogeneity, and its role in tumor progression and therapy resistance. Here, we consider not only genetic and epigenetic mechanisms, but also inflammation and cell state reprogramming in creating tumor heterogeneity. We discuss similarities between normal mammary epithelial developmental states and various breast cancer molecular sub-types, and the cells that are thought to propagate them. We emphasize that while stem cell phenotypes and mesenchymal character have often been conflated, existing data suggest that the combination of intrinsic genetic and epigenetic changes, and microenvironmental influences generate multiple types of tumor propagating cells distinguishable by their positions along a continuum of epithelial to mesenchymal, stem to differentiated and embryonic to mature cell states. Consequently, in addition to the prospect of stem cell-directed tumor therapies, there is a need to understand interrelationships between stem cell, epithelial–mesenchymal, and tumor-associated reprogramming events to develop new therapies that mitigate cell state plasticity and minimize the evolution of tumor heterogeneity.Geoffrey M. WahlBenjamin T. SpikeNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 3, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Geoffrey M. Wahl Benjamin T. Spike Cell state plasticity, stem cells, EMT, and the generation of intra-tumoral heterogeneity
description	Abstract Cellular heterogeneity in cancer represents a significant challenge. In order to develop effective and lasting therapies, it is essential to understand the source of this heterogeneity, and its role in tumor progression and therapy resistance. Here, we consider not only genetic and epigenetic mechanisms, but also inflammation and cell state reprogramming in creating tumor heterogeneity. We discuss similarities between normal mammary epithelial developmental states and various breast cancer molecular sub-types, and the cells that are thought to propagate them. We emphasize that while stem cell phenotypes and mesenchymal character have often been conflated, existing data suggest that the combination of intrinsic genetic and epigenetic changes, and microenvironmental influences generate multiple types of tumor propagating cells distinguishable by their positions along a continuum of epithelial to mesenchymal, stem to differentiated and embryonic to mature cell states. Consequently, in addition to the prospect of stem cell-directed tumor therapies, there is a need to understand interrelationships between stem cell, epithelial–mesenchymal, and tumor-associated reprogramming events to develop new therapies that mitigate cell state plasticity and minimize the evolution of tumor heterogeneity.
format	article
author	Geoffrey M. Wahl Benjamin T. Spike
author_facet	Geoffrey M. Wahl Benjamin T. Spike
author_sort	Geoffrey M. Wahl
title	Cell state plasticity, stem cells, EMT, and the generation of intra-tumoral heterogeneity
title_short	Cell state plasticity, stem cells, EMT, and the generation of intra-tumoral heterogeneity
title_full	Cell state plasticity, stem cells, EMT, and the generation of intra-tumoral heterogeneity
title_fullStr	Cell state plasticity, stem cells, EMT, and the generation of intra-tumoral heterogeneity
title_full_unstemmed	Cell state plasticity, stem cells, EMT, and the generation of intra-tumoral heterogeneity
title_sort	cell state plasticity, stem cells, emt, and the generation of intra-tumoral heterogeneity
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/657a1343dbc640d09e0f4e77d11190cc
work_keys_str_mv	AT geoffreymwahl cellstateplasticitystemcellsemtandthegenerationofintratumoralheterogeneity AT benjamintspike cellstateplasticitystemcellsemtandthegenerationofintratumoralheterogeneity
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Cell state plasticity, stem cells, EMT, and the generation of intra-tumoral heterogeneity

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