2. Academic Validation
  3. N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells

N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells

  • Cancer Cell. 2016 Apr 11;29(4):536-547. doi: 10.1016/j.ccell.2016.03.001.
John K Lee 1,  John W Phillips 2,  Bryan A Smith 2,  Jung Wook Park 2,  Tanya Stoyanova 2,  Erin F McCaffrey 2,  Robert Baertsch 3,  Artem Sokolov 3,  Justin G Meyerowitz 4,  Colleen Mathis 2,  Donghui Cheng 5,  Joshua M Stuart 3,  Kevan M Shokat 6,  W Clay Gustafson 7,  Jiaoti Huang 8,  Owen N Witte 9
Affiliations

Affiliations

  • 1 Division of Hematology and Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • 2 Department of Microbiology, Immunology, and Medical Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • 3 Center for Biomolecular Science and Engineering, Jack Baskin School of Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
  • 4 Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Departments of Neurology and Neurological Surgery, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • 5 Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • 6 Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • 7 Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Pediatrics, UCSF Benioff Children's Hospital, University of California, San Francisco, San Francisco, CA 94158, USA.
  • 8 Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • 9 Department of Microbiology, Immunology, and Medical Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: [email protected].
PMID: 27050099 DOI: 10.1016/j.ccell.2016.03.001
Abstract

MYCN amplification and overexpression are common in neuroendocrine prostate Cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated Akt1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarcinoma and NEPC can arise from a common epithelial clone. Further, N-Myc is required for tumor maintenance, and destabilization of N-Myc through Aurora A kinase inhibition reduces tumor burden. Our findings establish N-Myc as a driver of NEPC and a target for therapeutic intervention.

Figures
Products