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Twist1-induced epithelial-mesenchymal transition according to microsatellite instability status in colon cancer cells

Colorectal cancer (CRC) with microsatellite instability (MSI) may exhibit impaired epithelial-mesenchymal transition (EMT), but little is known about the underlying mechanisms of this phenomenon. In this study, we investigated the role of Twist1 and its downstream signaling cascades in EMT induction...

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Autores principales: Oh, Bo Young, Kim, So-Young, Lee, Yeo Song, Hong, Hye Kyung, Kim, Tae Won, Kim, Seok Hyung, Lee, Woo Yong, Cho, Yong Beom
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5302973/
https://www.ncbi.nlm.nih.gov/pubmed/27494849
http://dx.doi.org/10.18632/oncotarget.10974
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author Oh, Bo Young
Kim, So-Young
Lee, Yeo Song
Hong, Hye Kyung
Kim, Tae Won
Kim, Seok Hyung
Lee, Woo Yong
Cho, Yong Beom
author_facet Oh, Bo Young
Kim, So-Young
Lee, Yeo Song
Hong, Hye Kyung
Kim, Tae Won
Kim, Seok Hyung
Lee, Woo Yong
Cho, Yong Beom
author_sort Oh, Bo Young
collection PubMed
description Colorectal cancer (CRC) with microsatellite instability (MSI) may exhibit impaired epithelial-mesenchymal transition (EMT), but little is known about the underlying mechanisms of this phenomenon. In this study, we investigated the role of Twist1 and its downstream signaling cascades in EMT induction according to MSI status. To investigate the effects of Twist1 on EMT induction according to MSI status, MSS LS513 and MSI LoVo colon cancer cell lines, which overexpress human Twist1, were generated. Twist1-induced EMT and its downstream signaling pathways were evaluated via in vitro and in vivo experiments. We found that Twist1 induced EMT markers and stem cell-like characteristics via AKT signaling pathways. Twist1 induced activation of AKT and suppression of glycogen synthase kinase (GSK)-3β, which resulted in the activation of β-catenin, increasing CD44 expression. In addition, Twist1 activated the AKT-induced NF-κB pathway, increasing CD44 and CD166 expression. Activation of both the AKT/GSK-3β/β-catenin and AKT/NF-κB pathways occurred in MSS LS513 cells, while only the AKT/GSK-3β/β-catenin pathway was activated in MSI LoVo cells. In conclusion, Twist1 induces stem cell-like characteristics in colon cancer cell lines related to EMT via AKT signaling pathways, and those pathways depend on MSI status.
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spelling pubmed-53029732017-02-13 Twist1-induced epithelial-mesenchymal transition according to microsatellite instability status in colon cancer cells Oh, Bo Young Kim, So-Young Lee, Yeo Song Hong, Hye Kyung Kim, Tae Won Kim, Seok Hyung Lee, Woo Yong Cho, Yong Beom Oncotarget Research Paper Colorectal cancer (CRC) with microsatellite instability (MSI) may exhibit impaired epithelial-mesenchymal transition (EMT), but little is known about the underlying mechanisms of this phenomenon. In this study, we investigated the role of Twist1 and its downstream signaling cascades in EMT induction according to MSI status. To investigate the effects of Twist1 on EMT induction according to MSI status, MSS LS513 and MSI LoVo colon cancer cell lines, which overexpress human Twist1, were generated. Twist1-induced EMT and its downstream signaling pathways were evaluated via in vitro and in vivo experiments. We found that Twist1 induced EMT markers and stem cell-like characteristics via AKT signaling pathways. Twist1 induced activation of AKT and suppression of glycogen synthase kinase (GSK)-3β, which resulted in the activation of β-catenin, increasing CD44 expression. In addition, Twist1 activated the AKT-induced NF-κB pathway, increasing CD44 and CD166 expression. Activation of both the AKT/GSK-3β/β-catenin and AKT/NF-κB pathways occurred in MSS LS513 cells, while only the AKT/GSK-3β/β-catenin pathway was activated in MSI LoVo cells. In conclusion, Twist1 induces stem cell-like characteristics in colon cancer cell lines related to EMT via AKT signaling pathways, and those pathways depend on MSI status. Impact Journals LLC 2016-08-01 /pmc/articles/PMC5302973/ /pubmed/27494849 http://dx.doi.org/10.18632/oncotarget.10974 Text en Copyright: © 2016 Oh 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
Oh, Bo Young
Kim, So-Young
Lee, Yeo Song
Hong, Hye Kyung
Kim, Tae Won
Kim, Seok Hyung
Lee, Woo Yong
Cho, Yong Beom
Twist1-induced epithelial-mesenchymal transition according to microsatellite instability status in colon cancer cells
title Twist1-induced epithelial-mesenchymal transition according to microsatellite instability status in colon cancer cells
title_full Twist1-induced epithelial-mesenchymal transition according to microsatellite instability status in colon cancer cells
title_fullStr Twist1-induced epithelial-mesenchymal transition according to microsatellite instability status in colon cancer cells
title_full_unstemmed Twist1-induced epithelial-mesenchymal transition according to microsatellite instability status in colon cancer cells
title_short Twist1-induced epithelial-mesenchymal transition according to microsatellite instability status in colon cancer cells
title_sort twist1-induced epithelial-mesenchymal transition according to microsatellite instability status in colon cancer cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5302973/
https://www.ncbi.nlm.nih.gov/pubmed/27494849
http://dx.doi.org/10.18632/oncotarget.10974
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