Title | N-Myc Induces an EZH2-Mediated Transcriptional Program Driving Neuroendocrine Prostate Cancer. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Dardenne E, Beltran H, Benelli M, Gayvert K, Berger A, Puca L, Cyrta J, Sboner A, Noorzad Z, MacDonald T, Cheung C, Yuen KShing, Gao D, Chen Y, Eilers M, Mosquera J-M, Robinson BD, Elemento O, Rubin MA, Demichelis F, Rickman DS |
Journal | Cancer Cell |
Volume | 30 |
Issue | 4 |
Pagination | 563-577 |
Date Published | 2016 10 10 |
ISSN | 1878-3686 |
Keywords | Animals, Azepines, Enhancer of Zeste Homolog 2 Protein, Genes, myc, Heterografts, Humans, Male, Mice, Mice, Transgenic, N-Myc Proto-Oncogene Protein, Neuroendocrine Tumors, Prostatic Neoplasms, Prostatic Neoplasms, Castration-Resistant, Protein Kinase Inhibitors, Pyrimidines, Signal Transduction, Transcription, Genetic |
Abstract | The transition from castration-resistant prostate adenocarcinoma (CRPC) to neuroendocrine prostate cancerĀ (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. |
DOI | 10.1016/j.ccell.2016.09.005 |
Alternate Journal | Cancer Cell |
PubMed ID | 27728805 |
PubMed Central ID | PMC5540451 |
Grant List | R01 CA179100 / CA / NCI NIH HHS / United States R01 CA193837 / CA / NCI NIH HHS / United States P50 CA092629 / CA / NCI NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States K08 CA140946 / CA / NCI NIH HHS / United States R01 CA116337 / CA / NCI NIH HHS / United States U01 CA111275 / CA / NCI NIH HHS / United States |