Androgen receptor regulates eIF5A2 expression and promotes prostate cancer metastasis via EMT

Abstract Androgen receptor (AR) is an androgen-activated transcription factor of the nuclear receptor superfamily. AR plays a role in the development and progression of prostate cancer (PCa). However, the exact role of AR in PCa metastasis remains unclear. In the present study, we aimed to elucidate...

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Autores principales:	Yuancai Zheng, Ping Li, Hang Huang, Xueting Ye, Wei Chen, Guodong Xu, Fangyi Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/a773eed3739a4adeaa41a3199fdc901d
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spelling	oai:doaj.org-article:a773eed3739a4adeaa41a3199fdc901d2021-12-05T12:08:28ZAndrogen receptor regulates eIF5A2 expression and promotes prostate cancer metastasis via EMT10.1038/s41420-021-00764-x2058-7716https://doaj.org/article/a773eed3739a4adeaa41a3199fdc901d2021-12-01T00:00:00Zhttps://doi.org/10.1038/s41420-021-00764-xhttps://doaj.org/toc/2058-7716Abstract Androgen receptor (AR) is an androgen-activated transcription factor of the nuclear receptor superfamily. AR plays a role in the development and progression of prostate cancer (PCa). However, the exact role of AR in PCa metastasis remains unclear. In the present study, we aimed to elucidate the function of AR in PCa. We found that eukaryotic translation initiation factor (EIF) 5A2, an elongation factor that induces epithelial-to-mesenchymal transition (EMT) in PCa cells, was significantly upregulated after 5α-dihydrotestosterone (DHT) stimulation and downregulated after anti‐androgen bicalutamide treatment in PCa cells with high AR expression, but not in cells with low AR expression. Moreover, eIF5A2 knockdown could eliminate DHT-induced invasion and migration of AR-positive PCa cells. DHT treatment decreased epithelial expression of E‐cadherin and β-catenin but increased the expression of the mesenchymal marker proteins Vimentin and N-cadherin. DHT therefore induced EMT, and knockdown of eIF5A2 inhibited DHT-induced EMT. Moreover, in vivo study, Luciferase signals from the lungs of the eIF5A2 plasmid group indicated higher metastasis ability, and the eIF5A2 siRNA group had lower metastasis ability. Our results suggest that AR positively regulates eIF5A2 expression in androgen-dependent cells, and stimulation of AR expression and signaling in prostate tumors promotes PCa metastasis by EMT induction and upregulation of eIF5A2.Yuancai ZhengPing LiHang HuangXueting YeWei ChenGuodong XuFangyi ZhangNature Publishing GrouparticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCell Death Discovery, Vol 7, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 Yuancai Zheng Ping Li Hang Huang Xueting Ye Wei Chen Guodong Xu Fangyi Zhang Androgen receptor regulates eIF5A2 expression and promotes prostate cancer metastasis via EMT
description	Abstract Androgen receptor (AR) is an androgen-activated transcription factor of the nuclear receptor superfamily. AR plays a role in the development and progression of prostate cancer (PCa). However, the exact role of AR in PCa metastasis remains unclear. In the present study, we aimed to elucidate the function of AR in PCa. We found that eukaryotic translation initiation factor (EIF) 5A2, an elongation factor that induces epithelial-to-mesenchymal transition (EMT) in PCa cells, was significantly upregulated after 5α-dihydrotestosterone (DHT) stimulation and downregulated after anti‐androgen bicalutamide treatment in PCa cells with high AR expression, but not in cells with low AR expression. Moreover, eIF5A2 knockdown could eliminate DHT-induced invasion and migration of AR-positive PCa cells. DHT treatment decreased epithelial expression of E‐cadherin and β-catenin but increased the expression of the mesenchymal marker proteins Vimentin and N-cadherin. DHT therefore induced EMT, and knockdown of eIF5A2 inhibited DHT-induced EMT. Moreover, in vivo study, Luciferase signals from the lungs of the eIF5A2 plasmid group indicated higher metastasis ability, and the eIF5A2 siRNA group had lower metastasis ability. Our results suggest that AR positively regulates eIF5A2 expression in androgen-dependent cells, and stimulation of AR expression and signaling in prostate tumors promotes PCa metastasis by EMT induction and upregulation of eIF5A2.
format	article
author	Yuancai Zheng Ping Li Hang Huang Xueting Ye Wei Chen Guodong Xu Fangyi Zhang
author_facet	Yuancai Zheng Ping Li Hang Huang Xueting Ye Wei Chen Guodong Xu Fangyi Zhang
author_sort	Yuancai Zheng
title	Androgen receptor regulates eIF5A2 expression and promotes prostate cancer metastasis via EMT
title_short	Androgen receptor regulates eIF5A2 expression and promotes prostate cancer metastasis via EMT
title_full	Androgen receptor regulates eIF5A2 expression and promotes prostate cancer metastasis via EMT
title_fullStr	Androgen receptor regulates eIF5A2 expression and promotes prostate cancer metastasis via EMT
title_full_unstemmed	Androgen receptor regulates eIF5A2 expression and promotes prostate cancer metastasis via EMT
title_sort	androgen receptor regulates eif5a2 expression and promotes prostate cancer metastasis via emt
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/a773eed3739a4adeaa41a3199fdc901d
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Androgen receptor regulates eIF5A2 expression and promotes prostate cancer metastasis via EMT

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