ISL1 promotes enzalutamide resistance in castration-resistant prostate cancer (CRPC) through epithelial to mesenchymal transition (EMT)

Abstract Abnormal expression of insulin gene enhancer-binding protein 1 (ISL1) has been demonstrated to be closely associated with cancer development and progression in several cancers. However, little is known about ISL1 expression in metastatic castration-resistant prostate cancer (CRPC). ISL1 has...

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Autores principales:	Jae Duck Choi, Tae Jin Kim, Byong Chang Jeong, Hwang Gyun Jeon, Seong Soo Jeon, Min Yong Kang, Seon Yong Yeom, Seong Il Seo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d22ade90b6634bf087ee7e38ce1223d9
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spelling	oai:doaj.org-article:d22ade90b6634bf087ee7e38ce1223d92021-11-14T12:18:39ZISL1 promotes enzalutamide resistance in castration-resistant prostate cancer (CRPC) through epithelial to mesenchymal transition (EMT)10.1038/s41598-021-01003-02045-2322https://doaj.org/article/d22ade90b6634bf087ee7e38ce1223d92021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01003-0https://doaj.org/toc/2045-2322Abstract Abnormal expression of insulin gene enhancer-binding protein 1 (ISL1) has been demonstrated to be closely associated with cancer development and progression in several cancers. However, little is known about ISL1 expression in metastatic castration-resistant prostate cancer (CRPC). ISL1 has also been recognized as a positive modulator of epithelial–mesenchymal transition (EMT). In this study, we focused on ISL1 which showed maximum upregulation at the mRNA level in the enzalutamide-resistant cell line. Accordingly, we found that ISL1 was overexpressed in enzalutamide-resistant C4-2B cells and its expression was significantly related to EMT. Our findings reveal the important role of ISL1 in androgen receptor (AR)-dependent prostate cancer cell growth; ISL1 knockdown reduced the AR activity and cell growth. ISL1 knockdown using small-interfering RNA inhibited AR, PSA, and EMT-related protein expression in C4-2B ENZR cells. In addition, knock-down ISL1 reduced the levels of AKT and p65 phosphorylation in C4-2B ENZR cells and these suggest that knock-down ISL1 suppresses EMT in part by targeting the AKT/NF-κB pathway. Further, ISL1 downregulation could effectively inhibit tumor growth in a human CRPC xenograft model. Together, the present study shows that downregulation of ISL1 expression is necessary for overcoming enzalutamide resistance and improving the survival of CRPC patients.Jae Duck ChoiTae Jin KimByong Chang JeongHwang Gyun JeonSeong Soo JeonMin Yong KangSeon Yong YeomSeong Il SeoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jae Duck Choi Tae Jin Kim Byong Chang Jeong Hwang Gyun Jeon Seong Soo Jeon Min Yong Kang Seon Yong Yeom Seong Il Seo ISL1 promotes enzalutamide resistance in castration-resistant prostate cancer (CRPC) through epithelial to mesenchymal transition (EMT)
description	Abstract Abnormal expression of insulin gene enhancer-binding protein 1 (ISL1) has been demonstrated to be closely associated with cancer development and progression in several cancers. However, little is known about ISL1 expression in metastatic castration-resistant prostate cancer (CRPC). ISL1 has also been recognized as a positive modulator of epithelial–mesenchymal transition (EMT). In this study, we focused on ISL1 which showed maximum upregulation at the mRNA level in the enzalutamide-resistant cell line. Accordingly, we found that ISL1 was overexpressed in enzalutamide-resistant C4-2B cells and its expression was significantly related to EMT. Our findings reveal the important role of ISL1 in androgen receptor (AR)-dependent prostate cancer cell growth; ISL1 knockdown reduced the AR activity and cell growth. ISL1 knockdown using small-interfering RNA inhibited AR, PSA, and EMT-related protein expression in C4-2B ENZR cells. In addition, knock-down ISL1 reduced the levels of AKT and p65 phosphorylation in C4-2B ENZR cells and these suggest that knock-down ISL1 suppresses EMT in part by targeting the AKT/NF-κB pathway. Further, ISL1 downregulation could effectively inhibit tumor growth in a human CRPC xenograft model. Together, the present study shows that downregulation of ISL1 expression is necessary for overcoming enzalutamide resistance and improving the survival of CRPC patients.
format	article
author	Jae Duck Choi Tae Jin Kim Byong Chang Jeong Hwang Gyun Jeon Seong Soo Jeon Min Yong Kang Seon Yong Yeom Seong Il Seo
author_facet	Jae Duck Choi Tae Jin Kim Byong Chang Jeong Hwang Gyun Jeon Seong Soo Jeon Min Yong Kang Seon Yong Yeom Seong Il Seo
author_sort	Jae Duck Choi
title	ISL1 promotes enzalutamide resistance in castration-resistant prostate cancer (CRPC) through epithelial to mesenchymal transition (EMT)
title_short	ISL1 promotes enzalutamide resistance in castration-resistant prostate cancer (CRPC) through epithelial to mesenchymal transition (EMT)
title_full	ISL1 promotes enzalutamide resistance in castration-resistant prostate cancer (CRPC) through epithelial to mesenchymal transition (EMT)
title_fullStr	ISL1 promotes enzalutamide resistance in castration-resistant prostate cancer (CRPC) through epithelial to mesenchymal transition (EMT)
title_full_unstemmed	ISL1 promotes enzalutamide resistance in castration-resistant prostate cancer (CRPC) through epithelial to mesenchymal transition (EMT)
title_sort	isl1 promotes enzalutamide resistance in castration-resistant prostate cancer (crpc) through epithelial to mesenchymal transition (emt)
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d22ade90b6634bf087ee7e38ce1223d9
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ISL1 promotes enzalutamide resistance in castration-resistant prostate cancer (CRPC) through epithelial to mesenchymal transition (EMT)

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