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Characterization of the CD49f(+)/CD44(+)/CD24(−) single-cell derived stem cell population in basal-like DCIS cells

The molecular mechanisms responsible for the Ductal Carcinoma in Situ (DCIS)-Invasive Ductal Carcinoma (IDC) transition have yet to be elucidated. Due to the lack of molecularly targeted therapies, basal-like DCIS has a high risk of recurrence and progression to invasive and metastatic cancers. In t...

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Autores principales: Duru, Nadire, Gernapudi, Ramkishore, Lo, Pang-Kuo, Yao, Yuan, Wolfson, Benjamin, Zhang, Yongshu, Zhou, Qun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216957/
https://www.ncbi.nlm.nih.gov/pubmed/27374087
http://dx.doi.org/10.18632/oncotarget.10203
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author Duru, Nadire
Gernapudi, Ramkishore
Lo, Pang-Kuo
Yao, Yuan
Wolfson, Benjamin
Zhang, Yongshu
Zhou, Qun
author_facet Duru, Nadire
Gernapudi, Ramkishore
Lo, Pang-Kuo
Yao, Yuan
Wolfson, Benjamin
Zhang, Yongshu
Zhou, Qun
author_sort Duru, Nadire
collection PubMed
description The molecular mechanisms responsible for the Ductal Carcinoma in Situ (DCIS)-Invasive Ductal Carcinoma (IDC) transition have yet to be elucidated. Due to the lack of molecularly targeted therapies, basal-like DCIS has a high risk of recurrence and progression to invasive and metastatic cancers. In this study, by applying a novel single-cell clonogenic approach with the CD49f(+)/CD44(+)/CD24(−) surface markers, we characterized the aggressive clones that have enhanced self-renewal, migratory and invasive capacities derived from a human DCIS model cell line MCF10DCIS. The aggressive clones had elevated ALDH1 activity, lower global DNA methylation and increased expression of stem cell related genes, especially concurrent activation of SOX2/OCT4. In addition, we showed that the aggressive clones have increased expression of lincRNA-RoR and miR-10b compared to non-aggressive clones, which enhance their self-renewal and invasive abilities. Finally, we confirmed our in vitro results in vivo, demonstrating that aggressive clones were capable of forming tumors in nude mice, whereas non-aggressive clones were not. Our data suggest that lincRNA-RoR and miR10b could be used to distinguish aggressive clones from non-aggressive clones within the heterogeneous CD49f(+)/CD44(+)/CD24(−) DCIS population. Our findings also provide the foundation to develop new chemoprevention agents for DCIS-IDC transition.
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spelling pubmed-52169572017-01-17 Characterization of the CD49f(+)/CD44(+)/CD24(−) single-cell derived stem cell population in basal-like DCIS cells Duru, Nadire Gernapudi, Ramkishore Lo, Pang-Kuo Yao, Yuan Wolfson, Benjamin Zhang, Yongshu Zhou, Qun Oncotarget Research Paper The molecular mechanisms responsible for the Ductal Carcinoma in Situ (DCIS)-Invasive Ductal Carcinoma (IDC) transition have yet to be elucidated. Due to the lack of molecularly targeted therapies, basal-like DCIS has a high risk of recurrence and progression to invasive and metastatic cancers. In this study, by applying a novel single-cell clonogenic approach with the CD49f(+)/CD44(+)/CD24(−) surface markers, we characterized the aggressive clones that have enhanced self-renewal, migratory and invasive capacities derived from a human DCIS model cell line MCF10DCIS. The aggressive clones had elevated ALDH1 activity, lower global DNA methylation and increased expression of stem cell related genes, especially concurrent activation of SOX2/OCT4. In addition, we showed that the aggressive clones have increased expression of lincRNA-RoR and miR-10b compared to non-aggressive clones, which enhance their self-renewal and invasive abilities. Finally, we confirmed our in vitro results in vivo, demonstrating that aggressive clones were capable of forming tumors in nude mice, whereas non-aggressive clones were not. Our data suggest that lincRNA-RoR and miR10b could be used to distinguish aggressive clones from non-aggressive clones within the heterogeneous CD49f(+)/CD44(+)/CD24(−) DCIS population. Our findings also provide the foundation to develop new chemoprevention agents for DCIS-IDC transition. Impact Journals LLC 2016-06-21 /pmc/articles/PMC5216957/ /pubmed/27374087 http://dx.doi.org/10.18632/oncotarget.10203 Text en Copyright: © 2016 Duru et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Duru, Nadire
Gernapudi, Ramkishore
Lo, Pang-Kuo
Yao, Yuan
Wolfson, Benjamin
Zhang, Yongshu
Zhou, Qun
Characterization of the CD49f(+)/CD44(+)/CD24(−) single-cell derived stem cell population in basal-like DCIS cells
title Characterization of the CD49f(+)/CD44(+)/CD24(−) single-cell derived stem cell population in basal-like DCIS cells
title_full Characterization of the CD49f(+)/CD44(+)/CD24(−) single-cell derived stem cell population in basal-like DCIS cells
title_fullStr Characterization of the CD49f(+)/CD44(+)/CD24(−) single-cell derived stem cell population in basal-like DCIS cells
title_full_unstemmed Characterization of the CD49f(+)/CD44(+)/CD24(−) single-cell derived stem cell population in basal-like DCIS cells
title_short Characterization of the CD49f(+)/CD44(+)/CD24(−) single-cell derived stem cell population in basal-like DCIS cells
title_sort characterization of the cd49f(+)/cd44(+)/cd24(−) single-cell derived stem cell population in basal-like dcis cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216957/
https://www.ncbi.nlm.nih.gov/pubmed/27374087
http://dx.doi.org/10.18632/oncotarget.10203
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