| Autor: |
Roosa Kaarijärvi, Heidi Kaljunen, Lucia Nappi, Ladan Fazli, Sonia H. Y. Kung, Jaana M. Hartikainen, Ville Paakinaho, Janne Capra, Kirsi Rilla, Marjo Malinen, Petri I. Mäkinen, Seppo Ylä-Herttuala, Amina Zoubeidi, Yuzhuo Wang, Martin E. Gleave, Mikko Hiltunen, Kirsi Ketola |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Communications Biology, Vol 7, Iss 1, Pp 1-13 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2399-3642 |
| DOI: |
10.1038/s42003-023-05741-x |
| Popis: |
Abstract Treatment-induced neuroendocrine prostate cancer (t-NEPC) is a lethal subtype of castration-resistant prostate cancer resistant to androgen receptor (AR) inhibitors. Our study unveils that AR suppresses the neuronal development protein dihydropyrimidinase-related protein 5 (DPYSL5), providing a mechanism for neuroendocrine transformation under androgen deprivation therapy. Our unique CRPC-NEPC cohort, comprising 135 patient tumor samples, including 55 t-NEPC patient samples, exhibits a high expression of DPYSL5 in t-NEPC patient tumors. DPYSL5 correlates with neuroendocrine-related markers and inversely with AR and PSA. DPYSL5 overexpression in prostate cancer cells induces a neuron-like phenotype, enhances invasion, proliferation, and upregulates stemness and neuroendocrine-related markers. Mechanistically, DPYSL5 promotes prostate cancer cell plasticity via EZH2-mediated PRC2 activation. Depletion of DPYSL5 decreases proliferation, induces G1 phase cell cycle arrest, reverses neuroendocrine phenotype, and upregulates luminal genes. In conclusion, DPYSL5 plays a critical role in regulating prostate cancer cell plasticity, and we propose the AR/DPYSL5/EZH2/PRC2 axis as a driver of t-NEPC progression. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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