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Feedforward loop between IMP1 and YAP/TAZ promotes tumorigenesis and malignant progression in glioblastoma

YAP/TAZ have been identified as master regulators in malignant phenotypes of glioblastoma (GBM); however, YAP/TAZ transcriptional disruptor in GBM treatment remains ineffective. Whether post‐transcriptional dysregulation of YAP/TAZ improves GBM outcome is currently unknown. Here, we report that insu...

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Autores principales: Yang, Jia, Wu, Xujia, Wang, Jia, Guo, Xing, Chen, Junju, Yang, Xuesong, Zhong, Jian, Li, Xixi, Deng, Zhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10154852/
https://www.ncbi.nlm.nih.gov/pubmed/36308276
http://dx.doi.org/10.1111/cas.15636
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author Yang, Jia
Wu, Xujia
Wang, Jia
Guo, Xing
Chen, Junju
Yang, Xuesong
Zhong, Jian
Li, Xixi
Deng, Zhong
author_facet Yang, Jia
Wu, Xujia
Wang, Jia
Guo, Xing
Chen, Junju
Yang, Xuesong
Zhong, Jian
Li, Xixi
Deng, Zhong
author_sort Yang, Jia
collection PubMed
description YAP/TAZ have been identified as master regulators in malignant phenotypes of glioblastoma (GBM); however, YAP/TAZ transcriptional disruptor in GBM treatment remains ineffective. Whether post‐transcriptional dysregulation of YAP/TAZ improves GBM outcome is currently unknown. Here, we report that insulin‐like growth factor 2 (IGF2) mRNA‐binding protein 1 (IGF2BP1 or IMP1) is upregulated in mesenchymal GBM compared with proneural GBM and correlates with worse patient outcome. Overexpression of IMP1 in proneural glioma stem‐like cells (GSCs) promotes while IMP1 knockdown in mesenchymal GSCs attenuates tumorigenesis and mesenchymal signatures. IMP1 binds to and stabilizes m6A‐YAP mRNA, leading to activation of YAP/TAZ signaling, depending on its m6A recognition and binding domain. On the other hand, TAZ functions as enhancer for IMP1 expression. Collectively, our data reveal a feedforward loop between IMP1 and YAP/TAZ maintaining GBM/GSC tumorigenesis and malignant progression and a promising molecular target in GBM.
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spelling pubmed-101548522023-05-04 Feedforward loop between IMP1 and YAP/TAZ promotes tumorigenesis and malignant progression in glioblastoma Yang, Jia Wu, Xujia Wang, Jia Guo, Xing Chen, Junju Yang, Xuesong Zhong, Jian Li, Xixi Deng, Zhong Cancer Sci ORIGINAL ARTICLES YAP/TAZ have been identified as master regulators in malignant phenotypes of glioblastoma (GBM); however, YAP/TAZ transcriptional disruptor in GBM treatment remains ineffective. Whether post‐transcriptional dysregulation of YAP/TAZ improves GBM outcome is currently unknown. Here, we report that insulin‐like growth factor 2 (IGF2) mRNA‐binding protein 1 (IGF2BP1 or IMP1) is upregulated in mesenchymal GBM compared with proneural GBM and correlates with worse patient outcome. Overexpression of IMP1 in proneural glioma stem‐like cells (GSCs) promotes while IMP1 knockdown in mesenchymal GSCs attenuates tumorigenesis and mesenchymal signatures. IMP1 binds to and stabilizes m6A‐YAP mRNA, leading to activation of YAP/TAZ signaling, depending on its m6A recognition and binding domain. On the other hand, TAZ functions as enhancer for IMP1 expression. Collectively, our data reveal a feedforward loop between IMP1 and YAP/TAZ maintaining GBM/GSC tumorigenesis and malignant progression and a promising molecular target in GBM. John Wiley and Sons Inc. 2023-03-01 /pmc/articles/PMC10154852/ /pubmed/36308276 http://dx.doi.org/10.1111/cas.15636 Text en © 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle ORIGINAL ARTICLES
Yang, Jia
Wu, Xujia
Wang, Jia
Guo, Xing
Chen, Junju
Yang, Xuesong
Zhong, Jian
Li, Xixi
Deng, Zhong
Feedforward loop between IMP1 and YAP/TAZ promotes tumorigenesis and malignant progression in glioblastoma
title Feedforward loop between IMP1 and YAP/TAZ promotes tumorigenesis and malignant progression in glioblastoma
title_full Feedforward loop between IMP1 and YAP/TAZ promotes tumorigenesis and malignant progression in glioblastoma
title_fullStr Feedforward loop between IMP1 and YAP/TAZ promotes tumorigenesis and malignant progression in glioblastoma
title_full_unstemmed Feedforward loop between IMP1 and YAP/TAZ promotes tumorigenesis and malignant progression in glioblastoma
title_short Feedforward loop between IMP1 and YAP/TAZ promotes tumorigenesis and malignant progression in glioblastoma
title_sort feedforward loop between imp1 and yap/taz promotes tumorigenesis and malignant progression in glioblastoma
topic ORIGINAL ARTICLES
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10154852/
https://www.ncbi.nlm.nih.gov/pubmed/36308276
http://dx.doi.org/10.1111/cas.15636
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