N-Myc Induces an EZH2-Mediated Transcriptional Program Driving Neuroendocrine Prostate Cancer.

Details

Serval ID
serval:BIB_B22207EF398F
Type
Article: article from journal or magazin.
Collection
Publications
Title
N-Myc Induces an EZH2-Mediated Transcriptional Program Driving Neuroendocrine Prostate Cancer.
Journal
Cancer cell
Author(s)
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.
ISSN
1878-3686 (Electronic)
ISSN-L
1535-6108
Publication state
Published
Issued date
10/10/2016
Peer-reviewed
Oui
Volume
30
Number
4
Pages
563-577
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
Publication Status: ppublish
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.
Keywords
Animals, Azepines/pharmacology, Enhancer of Zeste Homolog 2 Protein/antagonists & inhibitors, Enhancer of Zeste Homolog 2 Protein/genetics, Enhancer of Zeste Homolog 2 Protein/metabolism, Genes, myc, Heterografts, Humans, Male, Mice, Mice, Transgenic, N-Myc Proto-Oncogene Protein/biosynthesis, N-Myc Proto-Oncogene Protein/genetics, N-Myc Proto-Oncogene Protein/metabolism, Neuroendocrine Tumors/drug therapy, Neuroendocrine Tumors/genetics, Neuroendocrine Tumors/metabolism, Neuroendocrine Tumors/pathology, Prostatic Neoplasms/drug therapy, Prostatic Neoplasms/genetics, Prostatic Neoplasms/metabolism, Prostatic Neoplasms/pathology, Prostatic Neoplasms, Castration-Resistant/drug therapy, Prostatic Neoplasms, Castration-Resistant/genetics, Prostatic Neoplasms, Castration-Resistant/metabolism, Prostatic Neoplasms, Castration-Resistant/pathology, Protein Kinase Inhibitors/pharmacology, Pyrimidines/pharmacology, Signal Transduction, Transcription, Genetic, Aurora kinase A, EZH2, N-Myc, castration-resistant prostate adenocarcinoma, genetically engineered mouse, neuroendocrine prostate cancer, prostate cancer organoid
Pubmed
Web of science
Open Access
Yes
Create date
08/07/2020 11:24
Last modification date
16/07/2020 8:43
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