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The Wnt/β-catenin signaling/Id2 cascade mediates the effects of hypoxia on the hierarchy of colorectal-cancer stem cells

Hypoxia, a feature common to most solid tumors, is known to regulate many aspects of tumorigenesis. Recently, it was suggested that hypoxia increased the size of the cancer stem-cell (CSC) subpopulations and promoted the acquisition of a CSC-like phenotype. However, candidate hypoxia-regulated media...

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Autores principales: Dong, Hye-Jin, Jang, Gyu-Beom, Lee, Hwa-Yong, Park, Se-Ra, Kim, Ji-Young, Nam, Jeong-Seok, Hong, In-Sun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786801/
https://www.ncbi.nlm.nih.gov/pubmed/26965643
http://dx.doi.org/10.1038/srep22966
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author Dong, Hye-Jin
Jang, Gyu-Beom
Lee, Hwa-Yong
Park, Se-Ra
Kim, Ji-Young
Nam, Jeong-Seok
Hong, In-Sun
author_facet Dong, Hye-Jin
Jang, Gyu-Beom
Lee, Hwa-Yong
Park, Se-Ra
Kim, Ji-Young
Nam, Jeong-Seok
Hong, In-Sun
author_sort Dong, Hye-Jin
collection PubMed
description Hypoxia, a feature common to most solid tumors, is known to regulate many aspects of tumorigenesis. Recently, it was suggested that hypoxia increased the size of the cancer stem-cell (CSC) subpopulations and promoted the acquisition of a CSC-like phenotype. However, candidate hypoxia-regulated mediators specifically relevant to the stemness-related functions of colorectal CSCs have not been examined in detail. In the present study, we showed that hypoxia specifically promoted the self-renewal potential of CSCs. Through various in vitro studies, we found that hypoxia-induced Wnt/β-catenin signaling increased the occurrence of CSC-like phenotypes and the level of Id2 expression in colorectal-cancer cells. Importantly, the levels of hypoxia-induced CSC-sphere formation and Id2 expression were successfully attenuated by treatment with a Wnt/β-catenin-signaling inhibitor. We further demonstrated, for the first time, that the degree of hypoxia-induced CSC-sphere formation (CD44(+) subpopulation) in vitro and of tumor metastasis/dissemination in vivo were markedly suppressed by knocking down Id2 expression. Taken together, these data suggested that Wnt/β-catenin signaling mediated the hypoxia-induced self-renewal potential of colorectal-cancer CSCs through reactivating Id2 expression.
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spelling pubmed-47868012016-03-11 The Wnt/β-catenin signaling/Id2 cascade mediates the effects of hypoxia on the hierarchy of colorectal-cancer stem cells Dong, Hye-Jin Jang, Gyu-Beom Lee, Hwa-Yong Park, Se-Ra Kim, Ji-Young Nam, Jeong-Seok Hong, In-Sun Sci Rep Article Hypoxia, a feature common to most solid tumors, is known to regulate many aspects of tumorigenesis. Recently, it was suggested that hypoxia increased the size of the cancer stem-cell (CSC) subpopulations and promoted the acquisition of a CSC-like phenotype. However, candidate hypoxia-regulated mediators specifically relevant to the stemness-related functions of colorectal CSCs have not been examined in detail. In the present study, we showed that hypoxia specifically promoted the self-renewal potential of CSCs. Through various in vitro studies, we found that hypoxia-induced Wnt/β-catenin signaling increased the occurrence of CSC-like phenotypes and the level of Id2 expression in colorectal-cancer cells. Importantly, the levels of hypoxia-induced CSC-sphere formation and Id2 expression were successfully attenuated by treatment with a Wnt/β-catenin-signaling inhibitor. We further demonstrated, for the first time, that the degree of hypoxia-induced CSC-sphere formation (CD44(+) subpopulation) in vitro and of tumor metastasis/dissemination in vivo were markedly suppressed by knocking down Id2 expression. Taken together, these data suggested that Wnt/β-catenin signaling mediated the hypoxia-induced self-renewal potential of colorectal-cancer CSCs through reactivating Id2 expression. Nature Publishing Group 2016-03-11 /pmc/articles/PMC4786801/ /pubmed/26965643 http://dx.doi.org/10.1038/srep22966 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Dong, Hye-Jin
Jang, Gyu-Beom
Lee, Hwa-Yong
Park, Se-Ra
Kim, Ji-Young
Nam, Jeong-Seok
Hong, In-Sun
The Wnt/β-catenin signaling/Id2 cascade mediates the effects of hypoxia on the hierarchy of colorectal-cancer stem cells
title The Wnt/β-catenin signaling/Id2 cascade mediates the effects of hypoxia on the hierarchy of colorectal-cancer stem cells
title_full The Wnt/β-catenin signaling/Id2 cascade mediates the effects of hypoxia on the hierarchy of colorectal-cancer stem cells
title_fullStr The Wnt/β-catenin signaling/Id2 cascade mediates the effects of hypoxia on the hierarchy of colorectal-cancer stem cells
title_full_unstemmed The Wnt/β-catenin signaling/Id2 cascade mediates the effects of hypoxia on the hierarchy of colorectal-cancer stem cells
title_short The Wnt/β-catenin signaling/Id2 cascade mediates the effects of hypoxia on the hierarchy of colorectal-cancer stem cells
title_sort wnt/β-catenin signaling/id2 cascade mediates the effects of hypoxia on the hierarchy of colorectal-cancer stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786801/
https://www.ncbi.nlm.nih.gov/pubmed/26965643
http://dx.doi.org/10.1038/srep22966
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