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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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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. |
format | Online Article Text |
id | pubmed-10154852 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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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