RANKL immunisation inhibits prostate cancer metastasis by modulating EMT through a RANKL-dependent pathway

Abstract Prostate cancer (PCa) morbidity in the majority of patients is due to metastatic events, which are a clinical obstacle. Therefore, a better understanding of the mechanism underlying metastasis is imperative if we are to develop novel therapeutic strategies. Receptor activator of nuclear fac...

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Autores principales:	Mineon Park, Yong Jin Cho, Bora Kim, Young Jong Ko, Yuria Jang, Yeon Hee Moon, Hoon Hyun, Wonbong Lim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/af65c06b2e6b4f5390c60c729a4c4302
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spelling	oai:doaj.org-article:af65c06b2e6b4f5390c60c729a4c43022021-12-02T17:30:34ZRANKL immunisation inhibits prostate cancer metastasis by modulating EMT through a RANKL-dependent pathway10.1038/s41598-021-91721-22045-2322https://doaj.org/article/af65c06b2e6b4f5390c60c729a4c43022021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91721-2https://doaj.org/toc/2045-2322Abstract Prostate cancer (PCa) morbidity in the majority of patients is due to metastatic events, which are a clinical obstacle. Therefore, a better understanding of the mechanism underlying metastasis is imperative if we are to develop novel therapeutic strategies. Receptor activator of nuclear factor kappa-B (NF-κB) ligand (RANKL) regulates bone remodelling. Thus, agents that suppress RANKL signalling may be useful pharmacological treatments. Here, we used preclinical experimental models to investigate whether an inactive form of RANKL affects bone metastasis in RANKL-induced PCa. RANKL was associated with epithelial–mesenchymal transition (EMT) and expression of metastasis-related genes in PC3 cells. Therefore, we proposed a strategy to induce anti-cytokine antibodies using mutant RANKL as an immunogen. RANKL promoted migration and invasion of PC3 cells through EMT, and induced a significant increase in binding of β-catenin to TCF-4, an EMT-induced transcription factor in PCa cells, via mitogen-activated protein kinase and β-catenin/TCF-4 signalling. Thus, RANKL increased EMT and the metastatic properties of PC3 cells, suggesting a role as a therapeutic target to prevent PCa metastasis. Treatment with mutant RANKL reduced EMT and metastasis of PC3 PCa cells in an experimental metastasis model. Thus, mutant RANKL could serve as a potential vaccine to prevent and treat metastatic PCa.Mineon ParkYong Jin ChoBora KimYoung Jong KoYuria JangYeon Hee MoonHoon HyunWonbong LimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mineon Park Yong Jin Cho Bora Kim Young Jong Ko Yuria Jang Yeon Hee Moon Hoon Hyun Wonbong Lim RANKL immunisation inhibits prostate cancer metastasis by modulating EMT through a RANKL-dependent pathway
description	Abstract Prostate cancer (PCa) morbidity in the majority of patients is due to metastatic events, which are a clinical obstacle. Therefore, a better understanding of the mechanism underlying metastasis is imperative if we are to develop novel therapeutic strategies. Receptor activator of nuclear factor kappa-B (NF-κB) ligand (RANKL) regulates bone remodelling. Thus, agents that suppress RANKL signalling may be useful pharmacological treatments. Here, we used preclinical experimental models to investigate whether an inactive form of RANKL affects bone metastasis in RANKL-induced PCa. RANKL was associated with epithelial–mesenchymal transition (EMT) and expression of metastasis-related genes in PC3 cells. Therefore, we proposed a strategy to induce anti-cytokine antibodies using mutant RANKL as an immunogen. RANKL promoted migration and invasion of PC3 cells through EMT, and induced a significant increase in binding of β-catenin to TCF-4, an EMT-induced transcription factor in PCa cells, via mitogen-activated protein kinase and β-catenin/TCF-4 signalling. Thus, RANKL increased EMT and the metastatic properties of PC3 cells, suggesting a role as a therapeutic target to prevent PCa metastasis. Treatment with mutant RANKL reduced EMT and metastasis of PC3 PCa cells in an experimental metastasis model. Thus, mutant RANKL could serve as a potential vaccine to prevent and treat metastatic PCa.
format	article
author	Mineon Park Yong Jin Cho Bora Kim Young Jong Ko Yuria Jang Yeon Hee Moon Hoon Hyun Wonbong Lim
author_facet	Mineon Park Yong Jin Cho Bora Kim Young Jong Ko Yuria Jang Yeon Hee Moon Hoon Hyun Wonbong Lim
author_sort	Mineon Park
title	RANKL immunisation inhibits prostate cancer metastasis by modulating EMT through a RANKL-dependent pathway
title_short	RANKL immunisation inhibits prostate cancer metastasis by modulating EMT through a RANKL-dependent pathway
title_full	RANKL immunisation inhibits prostate cancer metastasis by modulating EMT through a RANKL-dependent pathway
title_fullStr	RANKL immunisation inhibits prostate cancer metastasis by modulating EMT through a RANKL-dependent pathway
title_full_unstemmed	RANKL immunisation inhibits prostate cancer metastasis by modulating EMT through a RANKL-dependent pathway
title_sort	rankl immunisation inhibits prostate cancer metastasis by modulating emt through a rankl-dependent pathway
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/af65c06b2e6b4f5390c60c729a4c4302
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RANKL immunisation inhibits prostate cancer metastasis by modulating EMT through a RANKL-dependent pathway

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