N-Myc induces an EZH2-mediated transcriptional program driving neuroendocrine prostate cancer Journal Article
| Authors: | Dardenne, E.; Beltran, H.; Benelli, M.; Gayvert, K.; Berger, A.; Puca, L.; Cyrta, J.; Sboner, A.; Noorzad, Z.; MacDonald, T.; Cheung, C.; Yuen, K. S.; Gao, D.; Chen, Y.; Eilers, M.; Mosquera, J. M.; Robinson, B. D.; Elemento, O.; Rubin, M. A.; Demichelis, F.; Rickman, D. S. |
| Article Title: | N-Myc induces an EZH2-mediated transcriptional program driving neuroendocrine prostate cancer |
| Abstract: | The transition from castration-resistant prostate adenocarcinoma (CRPC) to neuroendocrine prostate cancer (NEPC) has emerged as an important mechanism of treatment resistance. NEPC is associated with overexpression and gene amplification of MYCN (encoding N-Myc). N-Myc is an established oncogene in several rare pediatric tumors, but its role in prostate cancer progression is not well established. Integrating a genetically engineered mouse model and human prostate cancer transcriptome data, we show that N-Myc overexpression leads to the development of poorly differentiated, invasive prostate cancer that is molecularly similar to human NEPC. This includes an abrogation of androgen receptor signaling and induction of Polycomb Repressive Complex 2 signaling. Altogether, our data establishes N-Myc as an oncogenic driver of NEPC. © 2016 Elsevier Inc. |
| Keywords: | n-myc; ezh2; neuroendocrine prostate cancer; aurora kinase a; castration-resistant prostate adenocarcinoma; genetically engineered mouse; prostate cancer organoid |
| Journal Title: | Cancer Cell |
| Volume: | 30 |
| Issue: | 4 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2016-10-10 |
| Start Page: | 563 |
| End Page: | 577 |
| Language: | English |
| DOI: | 10.1016/j.ccell.2016.09.005 |
| PROVIDER: | scopus |
| PUBMED: | 27728805 |
| PMCID: | PMC5540451 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 November 2016 -- Source: Scopus |
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