All-Trans Retinoic Acid-Induced Deficiency of the Wnt/β-Catenin Pathway Enhances Hepatic Carcinoma Stem Cell Differentiation

Retinoic acid (RA) is an important biological signal that directly differentiates cells during embryonic development and tumorigenesis. However, the molecular mechanism of RA-mediated differentiation in hepatic cancer stem cells (hCSCs) is not well understood. In this study, we found that mRNA expre...

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Autores principales: Zhu, Xinfeng, Wang, Wenxue, Zhang, Xia, Bai, Jianhua, Chen, Gang, Li, Li, Li, Meizhang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4646487/
https://www.ncbi.nlm.nih.gov/pubmed/26571119
http://dx.doi.org/10.1371/journal.pone.0143255
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author Zhu, Xinfeng
Wang, Wenxue
Zhang, Xia
Bai, Jianhua
Chen, Gang
Li, Li
Li, Meizhang
author_facet Zhu, Xinfeng
Wang, Wenxue
Zhang, Xia
Bai, Jianhua
Chen, Gang
Li, Li
Li, Meizhang
author_sort Zhu, Xinfeng
collection PubMed
description Retinoic acid (RA) is an important biological signal that directly differentiates cells during embryonic development and tumorigenesis. However, the molecular mechanism of RA-mediated differentiation in hepatic cancer stem cells (hCSCs) is not well understood. In this study, we found that mRNA expressions of RA-biosynthesis-related dehydrogenases were highly expressed in hepatocellular carcinoma. All-trans retinoic acid (ATRA) differentiated hCSCs through inhibiting the function of β-catenin in vitro. ATRA also inhibited the function of PI3K-AKT and enhanced GSK-3β-dependent degradation of phosphorylated β-catenin. Furthermore, ATRA and β-catenin silencing both increased hCSC sensitivity to docetaxel treatment. Our results suggest that targeting β-catenin will provide extra benefits for ATRA-mediated treatment of hepatic cancer patients.
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spelling pubmed-46464872015-11-25 All-Trans Retinoic Acid-Induced Deficiency of the Wnt/β-Catenin Pathway Enhances Hepatic Carcinoma Stem Cell Differentiation Zhu, Xinfeng Wang, Wenxue Zhang, Xia Bai, Jianhua Chen, Gang Li, Li Li, Meizhang PLoS One Research Article Retinoic acid (RA) is an important biological signal that directly differentiates cells during embryonic development and tumorigenesis. However, the molecular mechanism of RA-mediated differentiation in hepatic cancer stem cells (hCSCs) is not well understood. In this study, we found that mRNA expressions of RA-biosynthesis-related dehydrogenases were highly expressed in hepatocellular carcinoma. All-trans retinoic acid (ATRA) differentiated hCSCs through inhibiting the function of β-catenin in vitro. ATRA also inhibited the function of PI3K-AKT and enhanced GSK-3β-dependent degradation of phosphorylated β-catenin. Furthermore, ATRA and β-catenin silencing both increased hCSC sensitivity to docetaxel treatment. Our results suggest that targeting β-catenin will provide extra benefits for ATRA-mediated treatment of hepatic cancer patients. Public Library of Science 2015-11-16 /pmc/articles/PMC4646487/ /pubmed/26571119 http://dx.doi.org/10.1371/journal.pone.0143255 Text en © 2015 Zhu et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Zhu, Xinfeng
Wang, Wenxue
Zhang, Xia
Bai, Jianhua
Chen, Gang
Li, Li
Li, Meizhang
All-Trans Retinoic Acid-Induced Deficiency of the Wnt/β-Catenin Pathway Enhances Hepatic Carcinoma Stem Cell Differentiation
title All-Trans Retinoic Acid-Induced Deficiency of the Wnt/β-Catenin Pathway Enhances Hepatic Carcinoma Stem Cell Differentiation
title_full All-Trans Retinoic Acid-Induced Deficiency of the Wnt/β-Catenin Pathway Enhances Hepatic Carcinoma Stem Cell Differentiation
title_fullStr All-Trans Retinoic Acid-Induced Deficiency of the Wnt/β-Catenin Pathway Enhances Hepatic Carcinoma Stem Cell Differentiation
title_full_unstemmed All-Trans Retinoic Acid-Induced Deficiency of the Wnt/β-Catenin Pathway Enhances Hepatic Carcinoma Stem Cell Differentiation
title_short All-Trans Retinoic Acid-Induced Deficiency of the Wnt/β-Catenin Pathway Enhances Hepatic Carcinoma Stem Cell Differentiation
title_sort all-trans retinoic acid-induced deficiency of the wnt/β-catenin pathway enhances hepatic carcinoma stem cell differentiation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4646487/
https://www.ncbi.nlm.nih.gov/pubmed/26571119
http://dx.doi.org/10.1371/journal.pone.0143255
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