TCF7L1 regulates cytokine response and neuroendocrine differentiation of prostate cancer

Abstract Neuroendocrine differentiation (NED) is associated with WNT signaling activation and can be significantly observed after failure of androgen-deprivation therapy (ADT) for prostatic adenocarcinomas. Cytokine signaling is stimulated in NED prostate cancer; however, how ADT-upregulated WNT sig...

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Autores principales:	Yu-Ching Wen, Yen-Nien Liu, Hsiu-Lien Yeh, Wei-Hao Chen, Kuo-Ching Jiang, Shian-Ren Lin, Jiaoti Huang, Michael Hsiao, Wei-Yu Chen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/99d5960710964c0a90f14edae6b01add
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spelling	oai:doaj.org-article:99d5960710964c0a90f14edae6b01add2021-11-21T12:15:24ZTCF7L1 regulates cytokine response and neuroendocrine differentiation of prostate cancer10.1038/s41389-021-00371-62157-9024https://doaj.org/article/99d5960710964c0a90f14edae6b01add2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41389-021-00371-6https://doaj.org/toc/2157-9024Abstract Neuroendocrine differentiation (NED) is associated with WNT signaling activation and can be significantly observed after failure of androgen-deprivation therapy (ADT) for prostatic adenocarcinomas. Cytokine signaling is stimulated in NED prostate cancer; however, how ADT-upregulated WNT signaling promotes activation of cytokine signaling and contributes to NED of prostate cancer is poorly understood. In this study, we identified ADT-mediated upregulation of transcription factor 7 like 1 (TCF7L1), which increases the cytokine response and enhances NED of prostate cancer through interleukin (IL)-8/C-X-C motif chemokine receptor type 2 (CXCR2) signaling activation. ADT induced the secretion of WNT4 which upon engagement of TCF7L1 in prostate cancer cells, enhanced IL-8 and CXCR2 expressions. TCF7L1 directly binds to the regulatory sequence region of IL-8 and CXCR2 through WNT4 activation, thus upregulating IL-8/CXCR2 signaling-driven NED and cell motility. Analysis of prostate tissue samples collected from small-cell neuroendocrine prostate cancer (SCPC) and castration-resistant prostate cancer (CRPC) tumors showed an increased intensity of nuclear TCF7L1 associated with CXCR2. Our results suggest that induction of WNT4/TCF7L1 results in increased NED and malignancy in prostate cancer that is linked to dysregulation of androgen receptor signaling and activation of the IL-8/CXCR2 pathway.Yu-Ching WenYen-Nien LiuHsiu-Lien YehWei-Hao ChenKuo-Ching JiangShian-Ren LinJiaoti HuangMichael HsiaoWei-Yu ChenNature Publishing GrouparticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENOncogenesis, Vol 10, Iss 11, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yu-Ching Wen Yen-Nien Liu Hsiu-Lien Yeh Wei-Hao Chen Kuo-Ching Jiang Shian-Ren Lin Jiaoti Huang Michael Hsiao Wei-Yu Chen TCF7L1 regulates cytokine response and neuroendocrine differentiation of prostate cancer
description	Abstract Neuroendocrine differentiation (NED) is associated with WNT signaling activation and can be significantly observed after failure of androgen-deprivation therapy (ADT) for prostatic adenocarcinomas. Cytokine signaling is stimulated in NED prostate cancer; however, how ADT-upregulated WNT signaling promotes activation of cytokine signaling and contributes to NED of prostate cancer is poorly understood. In this study, we identified ADT-mediated upregulation of transcription factor 7 like 1 (TCF7L1), which increases the cytokine response and enhances NED of prostate cancer through interleukin (IL)-8/C-X-C motif chemokine receptor type 2 (CXCR2) signaling activation. ADT induced the secretion of WNT4 which upon engagement of TCF7L1 in prostate cancer cells, enhanced IL-8 and CXCR2 expressions. TCF7L1 directly binds to the regulatory sequence region of IL-8 and CXCR2 through WNT4 activation, thus upregulating IL-8/CXCR2 signaling-driven NED and cell motility. Analysis of prostate tissue samples collected from small-cell neuroendocrine prostate cancer (SCPC) and castration-resistant prostate cancer (CRPC) tumors showed an increased intensity of nuclear TCF7L1 associated with CXCR2. Our results suggest that induction of WNT4/TCF7L1 results in increased NED and malignancy in prostate cancer that is linked to dysregulation of androgen receptor signaling and activation of the IL-8/CXCR2 pathway.
format	article
author	Yu-Ching Wen Yen-Nien Liu Hsiu-Lien Yeh Wei-Hao Chen Kuo-Ching Jiang Shian-Ren Lin Jiaoti Huang Michael Hsiao Wei-Yu Chen
author_facet	Yu-Ching Wen Yen-Nien Liu Hsiu-Lien Yeh Wei-Hao Chen Kuo-Ching Jiang Shian-Ren Lin Jiaoti Huang Michael Hsiao Wei-Yu Chen
author_sort	Yu-Ching Wen
title	TCF7L1 regulates cytokine response and neuroendocrine differentiation of prostate cancer
title_short	TCF7L1 regulates cytokine response and neuroendocrine differentiation of prostate cancer
title_full	TCF7L1 regulates cytokine response and neuroendocrine differentiation of prostate cancer
title_fullStr	TCF7L1 regulates cytokine response and neuroendocrine differentiation of prostate cancer
title_full_unstemmed	TCF7L1 regulates cytokine response and neuroendocrine differentiation of prostate cancer
title_sort	tcf7l1 regulates cytokine response and neuroendocrine differentiation of prostate cancer
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/99d5960710964c0a90f14edae6b01add
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TCF7L1 regulates cytokine response and neuroendocrine differentiation of prostate cancer

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