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Matrix softness regulates plasticity of tumour-repopulating cells via H3K9 demethylation and Sox2 expression

Tumour-repopulating cells (TRCs) are a self-renewing, tumorigenic subpopulation of cancer cells critical in cancer progression. However, the underlying mechanisms of how TRCs maintain their self-renewing capability remain elusive. Here we show that relatively undifferentiated melanoma TRCs exhibit p...

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Autores principales: Tan, Youhua, Tajik, Arash, Chen, Junwei, Jia, Qiong, Chowdhury, Farhan, Wang, Lili, Chen, Junjian, Zhang, Shuang, Hong, Ying, Yi, Haiying, Wu, Douglas C., Zhang, Yuejin, Wei, Fuxiang, Poh, Yeh-Chuin, Seong, Jihye, Singh, Rishi, Lin, Li-Jung, Doğanay, Sultan, Li, Yong, Jia, Haibo, Ha, Taekjip, Wang, Yingxiao, Huang, Bo, Wang, Ning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133791/
https://www.ncbi.nlm.nih.gov/pubmed/25099074
http://dx.doi.org/10.1038/ncomms5619
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author Tan, Youhua
Tajik, Arash
Chen, Junwei
Jia, Qiong
Chowdhury, Farhan
Wang, Lili
Chen, Junjian
Zhang, Shuang
Hong, Ying
Yi, Haiying
Wu, Douglas C.
Zhang, Yuejin
Wei, Fuxiang
Poh, Yeh-Chuin
Seong, Jihye
Singh, Rishi
Lin, Li-Jung
Doğanay, Sultan
Li, Yong
Jia, Haibo
Ha, Taekjip
Wang, Yingxiao
Huang, Bo
Wang, Ning
author_facet Tan, Youhua
Tajik, Arash
Chen, Junwei
Jia, Qiong
Chowdhury, Farhan
Wang, Lili
Chen, Junjian
Zhang, Shuang
Hong, Ying
Yi, Haiying
Wu, Douglas C.
Zhang, Yuejin
Wei, Fuxiang
Poh, Yeh-Chuin
Seong, Jihye
Singh, Rishi
Lin, Li-Jung
Doğanay, Sultan
Li, Yong
Jia, Haibo
Ha, Taekjip
Wang, Yingxiao
Huang, Bo
Wang, Ning
author_sort Tan, Youhua
collection PubMed
description Tumour-repopulating cells (TRCs) are a self-renewing, tumorigenic subpopulation of cancer cells critical in cancer progression. However, the underlying mechanisms of how TRCs maintain their self-renewing capability remain elusive. Here we show that relatively undifferentiated melanoma TRCs exhibit plasticity in Cdc42-mediated mechanical stiffening, histone 3 lysine residue 9 (H3K9) methylation, Sox2 expression and self-renewal capability. In contrast to differentiated melanoma cells, TRCs have a low level of H3K9 methylation that is unresponsive to matrix stiffness or applied forces. Silencing H3K9 methyltransferase G9a or SUV39h1 elevates the self-renewal capability of differentiated melanoma cells in a Sox2-dependent manner. Mechanistically, H3K9 methylation at the Sox2 promoter region inhibits Sox2 expression that is essential in maintaining self-renewal and tumorigenicity of TRCs both in vitro and in vivo. Taken together, our data suggest that 3D soft-fibrin-matrix-mediated cell softening, H3K9 demethylation and Sox2 gene expression are essential in regulating TRC self-renewal.
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spelling pubmed-41337912014-09-03 Matrix softness regulates plasticity of tumour-repopulating cells via H3K9 demethylation and Sox2 expression Tan, Youhua Tajik, Arash Chen, Junwei Jia, Qiong Chowdhury, Farhan Wang, Lili Chen, Junjian Zhang, Shuang Hong, Ying Yi, Haiying Wu, Douglas C. Zhang, Yuejin Wei, Fuxiang Poh, Yeh-Chuin Seong, Jihye Singh, Rishi Lin, Li-Jung Doğanay, Sultan Li, Yong Jia, Haibo Ha, Taekjip Wang, Yingxiao Huang, Bo Wang, Ning Nat Commun Article Tumour-repopulating cells (TRCs) are a self-renewing, tumorigenic subpopulation of cancer cells critical in cancer progression. However, the underlying mechanisms of how TRCs maintain their self-renewing capability remain elusive. Here we show that relatively undifferentiated melanoma TRCs exhibit plasticity in Cdc42-mediated mechanical stiffening, histone 3 lysine residue 9 (H3K9) methylation, Sox2 expression and self-renewal capability. In contrast to differentiated melanoma cells, TRCs have a low level of H3K9 methylation that is unresponsive to matrix stiffness or applied forces. Silencing H3K9 methyltransferase G9a or SUV39h1 elevates the self-renewal capability of differentiated melanoma cells in a Sox2-dependent manner. Mechanistically, H3K9 methylation at the Sox2 promoter region inhibits Sox2 expression that is essential in maintaining self-renewal and tumorigenicity of TRCs both in vitro and in vivo. Taken together, our data suggest that 3D soft-fibrin-matrix-mediated cell softening, H3K9 demethylation and Sox2 gene expression are essential in regulating TRC self-renewal. Nature Pub. Group 2014-08-06 /pmc/articles/PMC4133791/ /pubmed/25099074 http://dx.doi.org/10.1038/ncomms5619 Text en Copyright © 2014, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 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-nc-sa/4.0/
spellingShingle Article
Tan, Youhua
Tajik, Arash
Chen, Junwei
Jia, Qiong
Chowdhury, Farhan
Wang, Lili
Chen, Junjian
Zhang, Shuang
Hong, Ying
Yi, Haiying
Wu, Douglas C.
Zhang, Yuejin
Wei, Fuxiang
Poh, Yeh-Chuin
Seong, Jihye
Singh, Rishi
Lin, Li-Jung
Doğanay, Sultan
Li, Yong
Jia, Haibo
Ha, Taekjip
Wang, Yingxiao
Huang, Bo
Wang, Ning
Matrix softness regulates plasticity of tumour-repopulating cells via H3K9 demethylation and Sox2 expression
title Matrix softness regulates plasticity of tumour-repopulating cells via H3K9 demethylation and Sox2 expression
title_full Matrix softness regulates plasticity of tumour-repopulating cells via H3K9 demethylation and Sox2 expression
title_fullStr Matrix softness regulates plasticity of tumour-repopulating cells via H3K9 demethylation and Sox2 expression
title_full_unstemmed Matrix softness regulates plasticity of tumour-repopulating cells via H3K9 demethylation and Sox2 expression
title_short Matrix softness regulates plasticity of tumour-repopulating cells via H3K9 demethylation and Sox2 expression
title_sort matrix softness regulates plasticity of tumour-repopulating cells via h3k9 demethylation and sox2 expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133791/
https://www.ncbi.nlm.nih.gov/pubmed/25099074
http://dx.doi.org/10.1038/ncomms5619
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