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The significance of ErbB2/3 in the conversion of induced pluripotent stem cells into cancer stem cells

Cancer stem cells (CSCs) are suggested to be responsible for drug resistance and aggressive phenotypes of tumors. Mechanisms of CSC induction are still under investigation. Our lab has established a novel method to generate CSCs from iPSCs under a cancerous microenvironment mimicked by the condition...

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Autores principales: Hassan, Ghmkin, Zahra, Maram H., Seno, Akimasa, Seno, Masaharu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8854581/
https://www.ncbi.nlm.nih.gov/pubmed/35177646
http://dx.doi.org/10.1038/s41598-022-04980-y
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author Hassan, Ghmkin
Zahra, Maram H.
Seno, Akimasa
Seno, Masaharu
author_facet Hassan, Ghmkin
Zahra, Maram H.
Seno, Akimasa
Seno, Masaharu
author_sort Hassan, Ghmkin
collection PubMed
description Cancer stem cells (CSCs) are suggested to be responsible for drug resistance and aggressive phenotypes of tumors. Mechanisms of CSC induction are still under investigation. Our lab has established a novel method to generate CSCs from iPSCs under a cancerous microenvironment mimicked by the conditioned medium (CM) of cancer-derived cells. Here, we analyzed the transcriptome of CSCs, which were converted from iPSCs with CM from pancreatic ductal adenocarcinoma cells. The differentially expressed genes were identified and used to explore pathway enrichment. From the comparison of the CSCs with iPSCs, genes with elevated expression were related to the ErbB2/3 signaling pathway. Inhibition of either ErbB2 with lapatinib as a tyrosine kinase inhibitor or ErbB3 with TX1-85-1 or siRNAs arrested cell proliferation, inhibited the in vitro tumorigenicity, and lead to loss of stemness in the converting cells. The self-renewal and tube formation abilities of cells were also abolished while CD24 and Oct3/4 levels were reduced, and the MAPK pathway was overactivated. This study shows a potential involvement of the ErbB2/ErbB3 pathway in CSC generation and could lead to new insight into the mechanism of tumorigenesis and the way of cancer prevention.
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spelling pubmed-88545812022-02-18 The significance of ErbB2/3 in the conversion of induced pluripotent stem cells into cancer stem cells Hassan, Ghmkin Zahra, Maram H. Seno, Akimasa Seno, Masaharu Sci Rep Article Cancer stem cells (CSCs) are suggested to be responsible for drug resistance and aggressive phenotypes of tumors. Mechanisms of CSC induction are still under investigation. Our lab has established a novel method to generate CSCs from iPSCs under a cancerous microenvironment mimicked by the conditioned medium (CM) of cancer-derived cells. Here, we analyzed the transcriptome of CSCs, which were converted from iPSCs with CM from pancreatic ductal adenocarcinoma cells. The differentially expressed genes were identified and used to explore pathway enrichment. From the comparison of the CSCs with iPSCs, genes with elevated expression were related to the ErbB2/3 signaling pathway. Inhibition of either ErbB2 with lapatinib as a tyrosine kinase inhibitor or ErbB3 with TX1-85-1 or siRNAs arrested cell proliferation, inhibited the in vitro tumorigenicity, and lead to loss of stemness in the converting cells. The self-renewal and tube formation abilities of cells were also abolished while CD24 and Oct3/4 levels were reduced, and the MAPK pathway was overactivated. This study shows a potential involvement of the ErbB2/ErbB3 pathway in CSC generation and could lead to new insight into the mechanism of tumorigenesis and the way of cancer prevention. Nature Publishing Group UK 2022-02-17 /pmc/articles/PMC8854581/ /pubmed/35177646 http://dx.doi.org/10.1038/s41598-022-04980-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Hassan, Ghmkin
Zahra, Maram H.
Seno, Akimasa
Seno, Masaharu
The significance of ErbB2/3 in the conversion of induced pluripotent stem cells into cancer stem cells
title The significance of ErbB2/3 in the conversion of induced pluripotent stem cells into cancer stem cells
title_full The significance of ErbB2/3 in the conversion of induced pluripotent stem cells into cancer stem cells
title_fullStr The significance of ErbB2/3 in the conversion of induced pluripotent stem cells into cancer stem cells
title_full_unstemmed The significance of ErbB2/3 in the conversion of induced pluripotent stem cells into cancer stem cells
title_short The significance of ErbB2/3 in the conversion of induced pluripotent stem cells into cancer stem cells
title_sort significance of erbb2/3 in the conversion of induced pluripotent stem cells into cancer stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8854581/
https://www.ncbi.nlm.nih.gov/pubmed/35177646
http://dx.doi.org/10.1038/s41598-022-04980-y
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