N-Myc Induces an EZH2-Mediated Transcriptional Program Driving Neuroendocrine Prostate Cancer. Academic Article uri icon

Overview

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.

publication date

  • October 10, 2016

Research

keywords

  • Enhancer of Zeste Homolog 2 Protein
  • N-Myc Proto-Oncogene Protein
  • Neuroendocrine Tumors
  • Prostatic Neoplasms

Identity

PubMed Central ID

  • PMC5540451

Scopus Document Identifier

  • 84991790827

Digital Object Identifier (DOI)

  • 10.1016/j.ccell.2016.09.005

PubMed ID

  • 27728805

Additional Document Info

volume

  • 30

issue

  • 4