WDR4 promotes the progression and lymphatic metastasis of bladder cancer via transcriptional down-regulation of ARRB2

Lymph node (LN) metastasis is one of the key prognostic factors in bladder cancer, but its underlying mechanisms remain unclear. Here, we found that elevated expression of WD repeat domain 4 (WDR4) in bladder cancer correlated with worse prognosis. WDR4 can promote the LN metastasis and proliferatio...

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Autores principales: Wang, Guoli, He, Xin, Dai, Huiqi, Lin, Lingyi, Cao, Wenmin, Fu, Yao, Diao, Wenli, Ding, Meng, Zhang, Qing, Chen, Wei, Guo, Hongqian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10545698/
https://www.ncbi.nlm.nih.gov/pubmed/37783676
http://dx.doi.org/10.1038/s41389-023-00493-z
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author Wang, Guoli
He, Xin
Dai, Huiqi
Lin, Lingyi
Cao, Wenmin
Fu, Yao
Diao, Wenli
Ding, Meng
Zhang, Qing
Chen, Wei
Guo, Hongqian
author_facet Wang, Guoli
He, Xin
Dai, Huiqi
Lin, Lingyi
Cao, Wenmin
Fu, Yao
Diao, Wenli
Ding, Meng
Zhang, Qing
Chen, Wei
Guo, Hongqian
author_sort Wang, Guoli
collection PubMed
description Lymph node (LN) metastasis is one of the key prognostic factors in bladder cancer, but its underlying mechanisms remain unclear. Here, we found that elevated expression of WD repeat domain 4 (WDR4) in bladder cancer correlated with worse prognosis. WDR4 can promote the LN metastasis and proliferation of bladder cancer cells. Mechanistic studies showed that WDR4 can promote the nuclear localization of DEAD-box helicase 20 (DDX20) and act as an adaptor to bind DDX20 and Early growth response 1 (Egr1), thereby inhibiting Egr1-promoted transcriptional expression of arrestin beta 2 (ARRB2) and ultimately contributing to the progression of bladder cancer. Immunohistochemical analysis confirmed that WDR4 expression is also an independent predictor of LN metastasis in bladder cancer. Our results reveal a novel mechanism of LN metastasis and progression in bladder cancer and identify WDR4 as a potential therapeutic target for metastatic bladder cancer.
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spelling pubmed-105456982023-10-04 WDR4 promotes the progression and lymphatic metastasis of bladder cancer via transcriptional down-regulation of ARRB2 Wang, Guoli He, Xin Dai, Huiqi Lin, Lingyi Cao, Wenmin Fu, Yao Diao, Wenli Ding, Meng Zhang, Qing Chen, Wei Guo, Hongqian Oncogenesis Article Lymph node (LN) metastasis is one of the key prognostic factors in bladder cancer, but its underlying mechanisms remain unclear. Here, we found that elevated expression of WD repeat domain 4 (WDR4) in bladder cancer correlated with worse prognosis. WDR4 can promote the LN metastasis and proliferation of bladder cancer cells. Mechanistic studies showed that WDR4 can promote the nuclear localization of DEAD-box helicase 20 (DDX20) and act as an adaptor to bind DDX20 and Early growth response 1 (Egr1), thereby inhibiting Egr1-promoted transcriptional expression of arrestin beta 2 (ARRB2) and ultimately contributing to the progression of bladder cancer. Immunohistochemical analysis confirmed that WDR4 expression is also an independent predictor of LN metastasis in bladder cancer. Our results reveal a novel mechanism of LN metastasis and progression in bladder cancer and identify WDR4 as a potential therapeutic target for metastatic bladder cancer. Nature Publishing Group UK 2023-10-02 /pmc/articles/PMC10545698/ /pubmed/37783676 http://dx.doi.org/10.1038/s41389-023-00493-z Text en © The Author(s) 2023 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
Wang, Guoli
He, Xin
Dai, Huiqi
Lin, Lingyi
Cao, Wenmin
Fu, Yao
Diao, Wenli
Ding, Meng
Zhang, Qing
Chen, Wei
Guo, Hongqian
WDR4 promotes the progression and lymphatic metastasis of bladder cancer via transcriptional down-regulation of ARRB2
title WDR4 promotes the progression and lymphatic metastasis of bladder cancer via transcriptional down-regulation of ARRB2
title_full WDR4 promotes the progression and lymphatic metastasis of bladder cancer via transcriptional down-regulation of ARRB2
title_fullStr WDR4 promotes the progression and lymphatic metastasis of bladder cancer via transcriptional down-regulation of ARRB2
title_full_unstemmed WDR4 promotes the progression and lymphatic metastasis of bladder cancer via transcriptional down-regulation of ARRB2
title_short WDR4 promotes the progression and lymphatic metastasis of bladder cancer via transcriptional down-regulation of ARRB2
title_sort wdr4 promotes the progression and lymphatic metastasis of bladder cancer via transcriptional down-regulation of arrb2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10545698/
https://www.ncbi.nlm.nih.gov/pubmed/37783676
http://dx.doi.org/10.1038/s41389-023-00493-z
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