MCM2-7 complex is a novel druggable target for neuroendocrine prostate cancer

Abstract Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer that rarely develops de novo in primary tumors and is commonly acquired during the development of treatment resistance. NEPC is characterized by gain of neuroendocrine markers and loss of androgen receptor (AR), ma...

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Autores principales:	En-Chi Hsu, Michelle Shen, Merve Aslan, Shiqin Liu, Manoj Kumar, Fernando Garcia-Marques, Holly M. Nguyen, Rosalie Nolley, Sharon J. Pitteri, Eva Corey, James D. Brooks, Tanya Stoyanova
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0691e54f4cb8403ba947ac009a53d0a8
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spelling	oai:doaj.org-article:0691e54f4cb8403ba947ac009a53d0a82021-12-02T17:12:25ZMCM2-7 complex is a novel druggable target for neuroendocrine prostate cancer10.1038/s41598-021-92552-x2045-2322https://doaj.org/article/0691e54f4cb8403ba947ac009a53d0a82021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92552-xhttps://doaj.org/toc/2045-2322Abstract Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer that rarely develops de novo in primary tumors and is commonly acquired during the development of treatment resistance. NEPC is characterized by gain of neuroendocrine markers and loss of androgen receptor (AR), making it resistant to current therapeutic strategies targeting the AR signaling axis. Here, we report that MCM2, MCM3, MCM4, and MCM6 (MCM2/3/4/6) are elevated in human NEPC and high levels of MCM2/3/4/6 are associated with liver metastasis and poor survival in prostate cancer patients. MCM2/3/4/6 are four out of six proteins that form a core DNA helicase (MCM2-7) responsible for unwinding DNA forks during DNA replication. Inhibition of MCM2-7 by treatment with ciprofloxacin inhibits NEPC cell proliferation and migration in vitro, significantly delays NEPC tumor xenograft growth, and partially reverses the neuroendocrine phenotype in vivo. Our study reveals the clinical relevance of MCM2/3/4/6 proteins in NEPC and suggests that inhibition of MCM2-7 may represent a new therapeutic strategy for NEPC.En-Chi HsuMichelle ShenMerve AslanShiqin LiuManoj KumarFernando Garcia-MarquesHolly M. NguyenRosalie NolleySharon J. PitteriEva CoreyJames D. BrooksTanya StoyanovaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q En-Chi Hsu Michelle Shen Merve Aslan Shiqin Liu Manoj Kumar Fernando Garcia-Marques Holly M. Nguyen Rosalie Nolley Sharon J. Pitteri Eva Corey James D. Brooks Tanya Stoyanova MCM2-7 complex is a novel druggable target for neuroendocrine prostate cancer
description	Abstract Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer that rarely develops de novo in primary tumors and is commonly acquired during the development of treatment resistance. NEPC is characterized by gain of neuroendocrine markers and loss of androgen receptor (AR), making it resistant to current therapeutic strategies targeting the AR signaling axis. Here, we report that MCM2, MCM3, MCM4, and MCM6 (MCM2/3/4/6) are elevated in human NEPC and high levels of MCM2/3/4/6 are associated with liver metastasis and poor survival in prostate cancer patients. MCM2/3/4/6 are four out of six proteins that form a core DNA helicase (MCM2-7) responsible for unwinding DNA forks during DNA replication. Inhibition of MCM2-7 by treatment with ciprofloxacin inhibits NEPC cell proliferation and migration in vitro, significantly delays NEPC tumor xenograft growth, and partially reverses the neuroendocrine phenotype in vivo. Our study reveals the clinical relevance of MCM2/3/4/6 proteins in NEPC and suggests that inhibition of MCM2-7 may represent a new therapeutic strategy for NEPC.
format	article
author	En-Chi Hsu Michelle Shen Merve Aslan Shiqin Liu Manoj Kumar Fernando Garcia-Marques Holly M. Nguyen Rosalie Nolley Sharon J. Pitteri Eva Corey James D. Brooks Tanya Stoyanova
author_facet	En-Chi Hsu Michelle Shen Merve Aslan Shiqin Liu Manoj Kumar Fernando Garcia-Marques Holly M. Nguyen Rosalie Nolley Sharon J. Pitteri Eva Corey James D. Brooks Tanya Stoyanova
author_sort	En-Chi Hsu
title	MCM2-7 complex is a novel druggable target for neuroendocrine prostate cancer
title_short	MCM2-7 complex is a novel druggable target for neuroendocrine prostate cancer
title_full	MCM2-7 complex is a novel druggable target for neuroendocrine prostate cancer
title_fullStr	MCM2-7 complex is a novel druggable target for neuroendocrine prostate cancer
title_full_unstemmed	MCM2-7 complex is a novel druggable target for neuroendocrine prostate cancer
title_sort	mcm2-7 complex is a novel druggable target for neuroendocrine prostate cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0691e54f4cb8403ba947ac009a53d0a8
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MCM2-7 complex is a novel druggable target for neuroendocrine prostate cancer

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