Heterogeneity of subsets in glioblastoma mediated by Smad3 palmitoylation

Glioblastoma (GBM) is the most common and deadly of the primary intracranial tumors and is comprised of subsets that show plasticity and marked heterogeneity, contributing to the lack of success in genomic profiling to guide development of precision medicine for these tumors. In this study, a mutati...

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Autores principales: Fan, Xiaoqing, Fan, Junqi, Yang, Haoran, Zhao, Chenggang, Niu, Wanxiang, Fang, Zhiyou, Chen, Xueran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551152/
https://www.ncbi.nlm.nih.gov/pubmed/34707087
http://dx.doi.org/10.1038/s41389-021-00361-8
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author Fan, Xiaoqing
Fan, Junqi
Yang, Haoran
Zhao, Chenggang
Niu, Wanxiang
Fang, Zhiyou
Chen, Xueran
author_facet Fan, Xiaoqing
Fan, Junqi
Yang, Haoran
Zhao, Chenggang
Niu, Wanxiang
Fang, Zhiyou
Chen, Xueran
author_sort Fan, Xiaoqing
collection PubMed
description Glioblastoma (GBM) is the most common and deadly of the primary intracranial tumors and is comprised of subsets that show plasticity and marked heterogeneity, contributing to the lack of success in genomic profiling to guide development of precision medicine for these tumors. In this study, a mutation in isocitrate dehydrogenase 1 was found to suppress the transforming growth factor-beta signaling pathway and E2F4 interacted with Smad3 to inhibit expression of mesenchymal markers. However, palmitoylation of Smad3 mediated by palmitoyltransferase ZDHHC19 promoted activation of the transforming growth factor-beta signaling pathway, and its interaction with EP300 promoted expression of mesenchymal markers in the mesenchymal subtype of GBM. Smad3 and hypoxia-inducible factor 1-alpha may be important molecular targets for treatment of glioma because they appear to coordinate the basic aspects of cancer stem cell biology.
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spelling pubmed-85511522021-10-29 Heterogeneity of subsets in glioblastoma mediated by Smad3 palmitoylation Fan, Xiaoqing Fan, Junqi Yang, Haoran Zhao, Chenggang Niu, Wanxiang Fang, Zhiyou Chen, Xueran Oncogenesis Article Glioblastoma (GBM) is the most common and deadly of the primary intracranial tumors and is comprised of subsets that show plasticity and marked heterogeneity, contributing to the lack of success in genomic profiling to guide development of precision medicine for these tumors. In this study, a mutation in isocitrate dehydrogenase 1 was found to suppress the transforming growth factor-beta signaling pathway and E2F4 interacted with Smad3 to inhibit expression of mesenchymal markers. However, palmitoylation of Smad3 mediated by palmitoyltransferase ZDHHC19 promoted activation of the transforming growth factor-beta signaling pathway, and its interaction with EP300 promoted expression of mesenchymal markers in the mesenchymal subtype of GBM. Smad3 and hypoxia-inducible factor 1-alpha may be important molecular targets for treatment of glioma because they appear to coordinate the basic aspects of cancer stem cell biology. Nature Publishing Group UK 2021-10-27 /pmc/articles/PMC8551152/ /pubmed/34707087 http://dx.doi.org/10.1038/s41389-021-00361-8 Text en © The Author(s) 2021, corrected publication 2021 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 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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Fan, Xiaoqing
Fan, Junqi
Yang, Haoran
Zhao, Chenggang
Niu, Wanxiang
Fang, Zhiyou
Chen, Xueran
Heterogeneity of subsets in glioblastoma mediated by Smad3 palmitoylation
title Heterogeneity of subsets in glioblastoma mediated by Smad3 palmitoylation
title_full Heterogeneity of subsets in glioblastoma mediated by Smad3 palmitoylation
title_fullStr Heterogeneity of subsets in glioblastoma mediated by Smad3 palmitoylation
title_full_unstemmed Heterogeneity of subsets in glioblastoma mediated by Smad3 palmitoylation
title_short Heterogeneity of subsets in glioblastoma mediated by Smad3 palmitoylation
title_sort heterogeneity of subsets in glioblastoma mediated by smad3 palmitoylation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551152/
https://www.ncbi.nlm.nih.gov/pubmed/34707087
http://dx.doi.org/10.1038/s41389-021-00361-8
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