Translocation of intracellular CD24 constitutes a triggering event for drug resistance in breast cancer

Abstract The capacity of tumor cells to shift dynamically between different states could be responsible for chemoresistance and has been commonly linked to the acquisition of stem cell properties. Here, we have evaluated the phenotype switching associated with drug resistance in breast cancer cell l...

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Autores principales:	Hugo Werner Huth, Thiago Castro-Gomes, Alfredo Miranda de Goes, Catherine Ropert
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a5d252d45e864c05a67714f2837e58c4
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spelling	oai:doaj.org-article:a5d252d45e864c05a67714f2837e58c42021-12-02T18:53:19ZTranslocation of intracellular CD24 constitutes a triggering event for drug resistance in breast cancer10.1038/s41598-021-96449-72045-2322https://doaj.org/article/a5d252d45e864c05a67714f2837e58c42021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96449-7https://doaj.org/toc/2045-2322Abstract The capacity of tumor cells to shift dynamically between different states could be responsible for chemoresistance and has been commonly linked to the acquisition of stem cell properties. Here, we have evaluated the phenotype switching associated with drug resistance in breast cancer cell lines and cell lineage obtained from Brazilian patients. We have highlighted the role of the cancer stem cell marker CD24 in the dynamics of cell plasticity and the acquirement of drug resistance. We showed that the translocation of CD24 from cytosol to cell membrane is a triggering event for the phenotype change of breast tumor cells exposed to drug stress. Here, we provide evidence that the phenotype switching is due to the presence of a cytosolic pool of CD24. Importantly, the cellular localization of CD24 was correlated with the changes in the dynamics of p38 MAPK activation. A strong and continuous phosphorylation of the p38 MAPK led to the overexpression of Bcl-2 after treatment in persistent cells presenting high density of CD24 on cell membrane. This phenotype enabled the cells to enter in slow-down of cell cycle, after which several weeks later, the dormant cells proliferated again. Importantly, the use of a p38 activity inhibitor sensitized cells to drug treatment and avoided chemoresistance.Hugo Werner HuthThiago Castro-GomesAlfredo Miranda de GoesCatherine RopertNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hugo Werner Huth Thiago Castro-Gomes Alfredo Miranda de Goes Catherine Ropert Translocation of intracellular CD24 constitutes a triggering event for drug resistance in breast cancer
description	Abstract The capacity of tumor cells to shift dynamically between different states could be responsible for chemoresistance and has been commonly linked to the acquisition of stem cell properties. Here, we have evaluated the phenotype switching associated with drug resistance in breast cancer cell lines and cell lineage obtained from Brazilian patients. We have highlighted the role of the cancer stem cell marker CD24 in the dynamics of cell plasticity and the acquirement of drug resistance. We showed that the translocation of CD24 from cytosol to cell membrane is a triggering event for the phenotype change of breast tumor cells exposed to drug stress. Here, we provide evidence that the phenotype switching is due to the presence of a cytosolic pool of CD24. Importantly, the cellular localization of CD24 was correlated with the changes in the dynamics of p38 MAPK activation. A strong and continuous phosphorylation of the p38 MAPK led to the overexpression of Bcl-2 after treatment in persistent cells presenting high density of CD24 on cell membrane. This phenotype enabled the cells to enter in slow-down of cell cycle, after which several weeks later, the dormant cells proliferated again. Importantly, the use of a p38 activity inhibitor sensitized cells to drug treatment and avoided chemoresistance.
format	article
author	Hugo Werner Huth Thiago Castro-Gomes Alfredo Miranda de Goes Catherine Ropert
author_facet	Hugo Werner Huth Thiago Castro-Gomes Alfredo Miranda de Goes Catherine Ropert
author_sort	Hugo Werner Huth
title	Translocation of intracellular CD24 constitutes a triggering event for drug resistance in breast cancer
title_short	Translocation of intracellular CD24 constitutes a triggering event for drug resistance in breast cancer
title_full	Translocation of intracellular CD24 constitutes a triggering event for drug resistance in breast cancer
title_fullStr	Translocation of intracellular CD24 constitutes a triggering event for drug resistance in breast cancer
title_full_unstemmed	Translocation of intracellular CD24 constitutes a triggering event for drug resistance in breast cancer
title_sort	translocation of intracellular cd24 constitutes a triggering event for drug resistance in breast cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a5d252d45e864c05a67714f2837e58c4
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_version_	1718377345095565312

Translocation of intracellular CD24 constitutes a triggering event for drug resistance in breast cancer

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