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Extracellular Acidification Induces Lysosomal Dysregulation

Many invasive cancers emerge through a years-long process of somatic evolution, characterized by an accumulation of heritable genetic and epigenetic changes and the emergence of increasingly aggressive clonal populations. In solid tumors, such as breast ductal carcinoma, the extracellular environmen...

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Detalles Bibliográficos
Autores principales: Ordway, Bryce, Gillies, Robert J., Damaghi, Mehdi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152284/
https://www.ncbi.nlm.nih.gov/pubmed/34067971
http://dx.doi.org/10.3390/cells10051188
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author Ordway, Bryce
Gillies, Robert J.
Damaghi, Mehdi
author_facet Ordway, Bryce
Gillies, Robert J.
Damaghi, Mehdi
author_sort Ordway, Bryce
collection PubMed
description Many invasive cancers emerge through a years-long process of somatic evolution, characterized by an accumulation of heritable genetic and epigenetic changes and the emergence of increasingly aggressive clonal populations. In solid tumors, such as breast ductal carcinoma, the extracellular environment for cells within the nascent tumor is harsh and imposes different types of stress on cells, such as hypoxia, nutrient deprivation, and cytokine inflammation. Acidosis is a constant stressor of most cancer cells due to its production through fermentation of glucose to lactic acid in hypoxic or normoxic regions (Warburg effect). Over a short period of time, acid stress can have a profound effect on the function of lysosomes within the cells exposed to this environment, and after long term exposure, lysosomal function of the cancer cells can become completely dysregulated. Whether this dysregulation is due to an epigenetic change or evolutionary selection has yet to be determined, but understanding the mechanisms behind this dysregulation could identify therapeutic opportunities.
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spelling pubmed-81522842021-05-27 Extracellular Acidification Induces Lysosomal Dysregulation Ordway, Bryce Gillies, Robert J. Damaghi, Mehdi Cells Brief Report Many invasive cancers emerge through a years-long process of somatic evolution, characterized by an accumulation of heritable genetic and epigenetic changes and the emergence of increasingly aggressive clonal populations. In solid tumors, such as breast ductal carcinoma, the extracellular environment for cells within the nascent tumor is harsh and imposes different types of stress on cells, such as hypoxia, nutrient deprivation, and cytokine inflammation. Acidosis is a constant stressor of most cancer cells due to its production through fermentation of glucose to lactic acid in hypoxic or normoxic regions (Warburg effect). Over a short period of time, acid stress can have a profound effect on the function of lysosomes within the cells exposed to this environment, and after long term exposure, lysosomal function of the cancer cells can become completely dysregulated. Whether this dysregulation is due to an epigenetic change or evolutionary selection has yet to be determined, but understanding the mechanisms behind this dysregulation could identify therapeutic opportunities. MDPI 2021-05-13 /pmc/articles/PMC8152284/ /pubmed/34067971 http://dx.doi.org/10.3390/cells10051188 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Ordway, Bryce
Gillies, Robert J.
Damaghi, Mehdi
Extracellular Acidification Induces Lysosomal Dysregulation
title Extracellular Acidification Induces Lysosomal Dysregulation
title_full Extracellular Acidification Induces Lysosomal Dysregulation
title_fullStr Extracellular Acidification Induces Lysosomal Dysregulation
title_full_unstemmed Extracellular Acidification Induces Lysosomal Dysregulation
title_short Extracellular Acidification Induces Lysosomal Dysregulation
title_sort extracellular acidification induces lysosomal dysregulation
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152284/
https://www.ncbi.nlm.nih.gov/pubmed/34067971
http://dx.doi.org/10.3390/cells10051188
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