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Soft fibrin matrix downregulates DAB2IP to promote Nanog-dependent growth of colon tumor-repopulating cells
Colon cancer stem cells (CSCs) have been shown to be responsible for the recurrence and metastasis of colorectal cancer (CRC). As a crucial microenvironmental factor, extracellular matrix (ECM) stiffness is known to affect the stemness of CSCs. Recently, fibrin deposition in the stroma of CRC was de...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377646/ https://www.ncbi.nlm.nih.gov/pubmed/30770783 http://dx.doi.org/10.1038/s41419-019-1309-7 |
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author | Zhang, Meng Xu, Cong Wang, Hai-zhou Peng, Ya-nan Li, Hai-ou Zhou, Yun-jiao Liu, Shi Wang, Fan Liu, Lan Chang, Ying Zhao, Qiu Liu, Jing |
author_facet | Zhang, Meng Xu, Cong Wang, Hai-zhou Peng, Ya-nan Li, Hai-ou Zhou, Yun-jiao Liu, Shi Wang, Fan Liu, Lan Chang, Ying Zhao, Qiu Liu, Jing |
author_sort | Zhang, Meng |
collection | PubMed |
description | Colon cancer stem cells (CSCs) have been shown to be responsible for the recurrence and metastasis of colorectal cancer (CRC). As a crucial microenvironmental factor, extracellular matrix (ECM) stiffness is known to affect the stemness of CSCs. Recently, fibrin deposition in the stroma of CRC was demonstrated to be responsible for tumor development. In this study, we used salmon fibrin gel to provide a 3D ECM for colon cancer cells and investigated its effects on cell growth as well as the underlying mechanisms. Compared with stiff 420 Pascal (Pa) and 1 050 Pa gels, 90 Pa soft fibrin gel was most efficient at isolating and enriching tumor colonies. The size and number of colony formation negatively correlated with gel stiffness. Specifically, these tumor colonies exhibited efficient tumorigenicity, upregulated stem cell markers, and had anti-chemotherapeutic properties and were thus named tumor-repopulating cells (TRCs). More importantly, the self-renewal molecule Nanog was sharply induced in 3D-cultured colon TRCs; further, Nanog siRNA significantly inhibited colony formation, suggesting the indispensable role of Nanog in TRC growth. A subsequent mechanistic study illustrated that Nanog expression could be modulated through fibrin gel stiffness-induced DAB2IP/PI3K/FOXA1 signaling in colon TRCs. |
format | Online Article Text |
id | pubmed-6377646 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63776462019-02-19 Soft fibrin matrix downregulates DAB2IP to promote Nanog-dependent growth of colon tumor-repopulating cells Zhang, Meng Xu, Cong Wang, Hai-zhou Peng, Ya-nan Li, Hai-ou Zhou, Yun-jiao Liu, Shi Wang, Fan Liu, Lan Chang, Ying Zhao, Qiu Liu, Jing Cell Death Dis Article Colon cancer stem cells (CSCs) have been shown to be responsible for the recurrence and metastasis of colorectal cancer (CRC). As a crucial microenvironmental factor, extracellular matrix (ECM) stiffness is known to affect the stemness of CSCs. Recently, fibrin deposition in the stroma of CRC was demonstrated to be responsible for tumor development. In this study, we used salmon fibrin gel to provide a 3D ECM for colon cancer cells and investigated its effects on cell growth as well as the underlying mechanisms. Compared with stiff 420 Pascal (Pa) and 1 050 Pa gels, 90 Pa soft fibrin gel was most efficient at isolating and enriching tumor colonies. The size and number of colony formation negatively correlated with gel stiffness. Specifically, these tumor colonies exhibited efficient tumorigenicity, upregulated stem cell markers, and had anti-chemotherapeutic properties and were thus named tumor-repopulating cells (TRCs). More importantly, the self-renewal molecule Nanog was sharply induced in 3D-cultured colon TRCs; further, Nanog siRNA significantly inhibited colony formation, suggesting the indispensable role of Nanog in TRC growth. A subsequent mechanistic study illustrated that Nanog expression could be modulated through fibrin gel stiffness-induced DAB2IP/PI3K/FOXA1 signaling in colon TRCs. Nature Publishing Group UK 2019-02-15 /pmc/articles/PMC6377646/ /pubmed/30770783 http://dx.doi.org/10.1038/s41419-019-1309-7 Text en © The Author(s) 2019 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Zhang, Meng Xu, Cong Wang, Hai-zhou Peng, Ya-nan Li, Hai-ou Zhou, Yun-jiao Liu, Shi Wang, Fan Liu, Lan Chang, Ying Zhao, Qiu Liu, Jing Soft fibrin matrix downregulates DAB2IP to promote Nanog-dependent growth of colon tumor-repopulating cells |
title | Soft fibrin matrix downregulates DAB2IP to promote Nanog-dependent growth of colon tumor-repopulating cells |
title_full | Soft fibrin matrix downregulates DAB2IP to promote Nanog-dependent growth of colon tumor-repopulating cells |
title_fullStr | Soft fibrin matrix downregulates DAB2IP to promote Nanog-dependent growth of colon tumor-repopulating cells |
title_full_unstemmed | Soft fibrin matrix downregulates DAB2IP to promote Nanog-dependent growth of colon tumor-repopulating cells |
title_short | Soft fibrin matrix downregulates DAB2IP to promote Nanog-dependent growth of colon tumor-repopulating cells |
title_sort | soft fibrin matrix downregulates dab2ip to promote nanog-dependent growth of colon tumor-repopulating cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377646/ https://www.ncbi.nlm.nih.gov/pubmed/30770783 http://dx.doi.org/10.1038/s41419-019-1309-7 |
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