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RNA-binding protein p54(nrb)/NONO potentiates nuclear EGFR-mediated tumorigenesis of triple-negative breast cancer
Nuclear-localized epidermal growth factor receptor (EGFR) highly correlates with the malignant progression and may be a promising therapeutic target for breast cancer. However, molecular mechanisms of nuclear EGFR in triple-negative breast cancer (TNBC) have not been fully elucidated. Here, we perfo...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8748691/ https://www.ncbi.nlm.nih.gov/pubmed/35013116 http://dx.doi.org/10.1038/s41419-021-04488-9 |
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author | Shen, Mengqin Zhang, Ruixue Jia, Wenzhi Zhu, Zongping Zhao, Li Huang, Gang Liu, Jianjun |
author_facet | Shen, Mengqin Zhang, Ruixue Jia, Wenzhi Zhu, Zongping Zhao, Li Huang, Gang Liu, Jianjun |
author_sort | Shen, Mengqin |
collection | PubMed |
description | Nuclear-localized epidermal growth factor receptor (EGFR) highly correlates with the malignant progression and may be a promising therapeutic target for breast cancer. However, molecular mechanisms of nuclear EGFR in triple-negative breast cancer (TNBC) have not been fully elucidated. Here, we performed gene-annotation enrichment analysis for the interactors of nuclear EGFR and found that RNA-binding proteins (RBPs) were closely associated with nuclear EGFR. We further demonstrated p54(nrb)/NONO, one of the RBPs, significantly interacted with nuclear EGFR. NONO was upregulated in 80 paired TNBC tissues and indicated a poor prognosis. Furthermore, NONO knockout significantly inhibited TNBC proliferation in vitro and in vivo. Mechanistically, NONO increased the stability of nuclear EGFR and recruited CREB binding protein (CBP) and its accompanying E1A binding protein p300, thereby enhancing the transcriptional activity of EGFR. In turn, EGFR positively regulated the affinity of NONO to mRNAs of nuclear EGFR downstream genes. Furthermore, the results indicated that the nuclear EGFR/NONO complex played a critical role in tumorigenesis and chemotherapy resistance. Taken together, our findings indicate that NONO enhances nuclear EGFR-mediated tumorigenesis and may be a potential therapeutic target for TNBC patients with nuclear EGFR expression. |
format | Online Article Text |
id | pubmed-8748691 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-87486912022-01-20 RNA-binding protein p54(nrb)/NONO potentiates nuclear EGFR-mediated tumorigenesis of triple-negative breast cancer Shen, Mengqin Zhang, Ruixue Jia, Wenzhi Zhu, Zongping Zhao, Li Huang, Gang Liu, Jianjun Cell Death Dis Article Nuclear-localized epidermal growth factor receptor (EGFR) highly correlates with the malignant progression and may be a promising therapeutic target for breast cancer. However, molecular mechanisms of nuclear EGFR in triple-negative breast cancer (TNBC) have not been fully elucidated. Here, we performed gene-annotation enrichment analysis for the interactors of nuclear EGFR and found that RNA-binding proteins (RBPs) were closely associated with nuclear EGFR. We further demonstrated p54(nrb)/NONO, one of the RBPs, significantly interacted with nuclear EGFR. NONO was upregulated in 80 paired TNBC tissues and indicated a poor prognosis. Furthermore, NONO knockout significantly inhibited TNBC proliferation in vitro and in vivo. Mechanistically, NONO increased the stability of nuclear EGFR and recruited CREB binding protein (CBP) and its accompanying E1A binding protein p300, thereby enhancing the transcriptional activity of EGFR. In turn, EGFR positively regulated the affinity of NONO to mRNAs of nuclear EGFR downstream genes. Furthermore, the results indicated that the nuclear EGFR/NONO complex played a critical role in tumorigenesis and chemotherapy resistance. Taken together, our findings indicate that NONO enhances nuclear EGFR-mediated tumorigenesis and may be a potential therapeutic target for TNBC patients with nuclear EGFR expression. Nature Publishing Group UK 2022-01-10 /pmc/articles/PMC8748691/ /pubmed/35013116 http://dx.doi.org/10.1038/s41419-021-04488-9 Text en © The Author(s) 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 Shen, Mengqin Zhang, Ruixue Jia, Wenzhi Zhu, Zongping Zhao, Li Huang, Gang Liu, Jianjun RNA-binding protein p54(nrb)/NONO potentiates nuclear EGFR-mediated tumorigenesis of triple-negative breast cancer |
title | RNA-binding protein p54(nrb)/NONO potentiates nuclear EGFR-mediated tumorigenesis of triple-negative breast cancer |
title_full | RNA-binding protein p54(nrb)/NONO potentiates nuclear EGFR-mediated tumorigenesis of triple-negative breast cancer |
title_fullStr | RNA-binding protein p54(nrb)/NONO potentiates nuclear EGFR-mediated tumorigenesis of triple-negative breast cancer |
title_full_unstemmed | RNA-binding protein p54(nrb)/NONO potentiates nuclear EGFR-mediated tumorigenesis of triple-negative breast cancer |
title_short | RNA-binding protein p54(nrb)/NONO potentiates nuclear EGFR-mediated tumorigenesis of triple-negative breast cancer |
title_sort | rna-binding protein p54(nrb)/nono potentiates nuclear egfr-mediated tumorigenesis of triple-negative breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8748691/ https://www.ncbi.nlm.nih.gov/pubmed/35013116 http://dx.doi.org/10.1038/s41419-021-04488-9 |
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