Sympathetic signaling facilitates progression of neuroendocrine prostate cancer

Abstract The progression of prostate cancer (PC) into neuroendocrine prostate cancer (NEPC) is a major challenge in treating PC. In NEPC, the PC cells undergo neuroendocrine differentiation (NED); however, the exact molecular mechanism that triggers NED is unknown. Peripheral nerves are recently sho...

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Autores principales:	Shubham Dwivedi, Maricris Bautista, Sanskriti Shrestha, Hussain Elhasasna, Tanaya Chaphekar, Frederick S. Vizeacoumar, Anand Krishnan
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/92fc736a598e4528bf6547bb3216d285
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spelling	oai:doaj.org-article:92fc736a598e4528bf6547bb3216d2852021-11-28T12:10:36ZSympathetic signaling facilitates progression of neuroendocrine prostate cancer10.1038/s41420-021-00752-12058-7716https://doaj.org/article/92fc736a598e4528bf6547bb3216d2852021-11-01T00:00:00Zhttps://doi.org/10.1038/s41420-021-00752-1https://doaj.org/toc/2058-7716Abstract The progression of prostate cancer (PC) into neuroendocrine prostate cancer (NEPC) is a major challenge in treating PC. In NEPC, the PC cells undergo neuroendocrine differentiation (NED); however, the exact molecular mechanism that triggers NED is unknown. Peripheral nerves are recently shown to promote PC. However, their contribution to NEPC was not studied well. In this study, we explored whether sympathetic neurosignaling contributes to NED. We found that human prostate tumors from patients that later developed metastases and castration-resistant prostate cancer (CRPC), a stage preceding to NEPC, have high sympathetic innervations. Our work revealed that high concentrations of the sympathetic neurotransmitter norepinephrine (NE) induces NED-like changes in PC cells in vitro, evident by their characteristic cellular and molecular changes. The NE-mediated NED was effectively inhibited by the Adrβ2 blocker propranolol. Strikingly, propranolol along with castration also significantly inhibited the development and progression of NEPC in vivo in an orthotopic NEPC model. Altogether, our results indicate that the NE-Adrβ2 axis is a potential therapeutic intervention point for NEPC.Shubham DwivediMaricris BautistaSanskriti ShresthaHussain ElhasasnaTanaya ChaphekarFrederick S. VizeacoumarAnand KrishnanNature 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 Shubham Dwivedi Maricris Bautista Sanskriti Shrestha Hussain Elhasasna Tanaya Chaphekar Frederick S. Vizeacoumar Anand Krishnan Sympathetic signaling facilitates progression of neuroendocrine prostate cancer
description	Abstract The progression of prostate cancer (PC) into neuroendocrine prostate cancer (NEPC) is a major challenge in treating PC. In NEPC, the PC cells undergo neuroendocrine differentiation (NED); however, the exact molecular mechanism that triggers NED is unknown. Peripheral nerves are recently shown to promote PC. However, their contribution to NEPC was not studied well. In this study, we explored whether sympathetic neurosignaling contributes to NED. We found that human prostate tumors from patients that later developed metastases and castration-resistant prostate cancer (CRPC), a stage preceding to NEPC, have high sympathetic innervations. Our work revealed that high concentrations of the sympathetic neurotransmitter norepinephrine (NE) induces NED-like changes in PC cells in vitro, evident by their characteristic cellular and molecular changes. The NE-mediated NED was effectively inhibited by the Adrβ2 blocker propranolol. Strikingly, propranolol along with castration also significantly inhibited the development and progression of NEPC in vivo in an orthotopic NEPC model. Altogether, our results indicate that the NE-Adrβ2 axis is a potential therapeutic intervention point for NEPC.
format	article
author	Shubham Dwivedi Maricris Bautista Sanskriti Shrestha Hussain Elhasasna Tanaya Chaphekar Frederick S. Vizeacoumar Anand Krishnan
author_facet	Shubham Dwivedi Maricris Bautista Sanskriti Shrestha Hussain Elhasasna Tanaya Chaphekar Frederick S. Vizeacoumar Anand Krishnan
author_sort	Shubham Dwivedi
title	Sympathetic signaling facilitates progression of neuroendocrine prostate cancer
title_short	Sympathetic signaling facilitates progression of neuroendocrine prostate cancer
title_full	Sympathetic signaling facilitates progression of neuroendocrine prostate cancer
title_fullStr	Sympathetic signaling facilitates progression of neuroendocrine prostate cancer
title_full_unstemmed	Sympathetic signaling facilitates progression of neuroendocrine prostate cancer
title_sort	sympathetic signaling facilitates progression of neuroendocrine prostate cancer
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/92fc736a598e4528bf6547bb3216d285
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Sympathetic signaling facilitates progression of neuroendocrine prostate cancer

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