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Nat Commun. 2018 Dec 5;9(1):5201. doi: 10.1038/s41467-018-07511-4.

NSD2 is a conserved driver of metastatic prostate cancer progression.

Author information

1
Department of Urology, Columbia University Irving Medical Center, 160 Fort Washington Ave, New York, NY, 10032, USA. aaytes@idibell.cat.
2
Programs of Molecular Mechanisms and Experimental Therapeutics in Oncology (ONCOBell), and Cancer Therapeutics Resistance (ProCURE), Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research, L'Hospitalet de Llobregat, Gran Via de L'Hospitalet, 199, 08908, Barcelona, Spain. aaytes@idibell.cat.
3
Department of Urology, Columbia University Irving Medical Center, 160 Fort Washington Ave, New York, NY, 10032, USA.
4
Department of Medicine, Columbia University Irving Medical Center, 630W 168th Street, New York, NY, 10032, USA.
5
Department of Systems Biology, Columbia University Irving Medical Center, 1130 Saint Nicholas Ave, New York, NY, 10032, USA.
6
Department of Health Informatics, Rutgers School of Health Professions, Rutgers, The State University of New Jersey, 65 Bergen Street, Newark, NJ, 07101, USA.
7
Programs of Molecular Mechanisms and Experimental Therapeutics in Oncology (ONCOBell), and Cancer Therapeutics Resistance (ProCURE), Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research, L'Hospitalet de Llobregat, Gran Via de L'Hospitalet, 199, 08908, Barcelona, Spain.
8
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY, 10065, USA.
9
Department for BioMedical Research, University of Bern, Murtenstrasse 35, CH-3008, Bern, Switzerland.
10
Department of Genetics and Development, Columbia University Irving Medical Center, 701 West 168th Street, New York, NY, 10032, USA.
11
Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, 1130 Saint Nicholas Ave, New York, NY, 10032, USA.
12
Department of Systems Biology, Columbia University Irving Medical Center, 1130 Saint Nicholas Ave, New York, NY, 10032, USA. ac2248@cumc.columbia.edu.
13
Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, 1130 Saint Nicholas Ave, New York, NY, 10032, USA. ac2248@cumc.columbia.edu.
14
Department of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, 701 West 168th Street, New York, NY, 10032, USA. ac2248@cumc.columbia.edu.
15
Department of Urology, Columbia University Irving Medical Center, 160 Fort Washington Ave, New York, NY, 10032, USA. cabateshen@columbia.edu.
16
Department of Medicine, Columbia University Irving Medical Center, 630W 168th Street, New York, NY, 10032, USA. cabateshen@columbia.edu.
17
Department of Systems Biology, Columbia University Irving Medical Center, 1130 Saint Nicholas Ave, New York, NY, 10032, USA. cabateshen@columbia.edu.
18
Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, 1130 Saint Nicholas Ave, New York, NY, 10032, USA. cabateshen@columbia.edu.
19
Department of Pathology and Cell Biology, Columbia University Irving Medical Center, 630W 168th Street, New York, NY, 10032, USA. cabateshen@columbia.edu.

Abstract

Deciphering cell-intrinsic mechanisms of metastasis progression in vivo is essential to identify novel therapeutic approaches. Here we elucidate cell-intrinsic drivers of metastatic prostate cancer progression through analyses of genetically engineered mouse models (GEMM) and correlative studies of human prostate cancer. Expression profiling of lineage-marked cells from mouse primary tumors and metastases defines a signature of de novo metastatic progression. Cross-species master regulator analyses comparing this mouse signature with a comparable human signature identifies conserved drivers of metastatic progression with demonstrable clinical and functional relevance. In particular, nuclear receptor binding SET Domain Protein 2 (NSD2) is robustly expressed in lethal prostate cancer in humans, while its silencing inhibits metastasis of mouse allografts in vivo. We propose that cross-species analysis can elucidate mechanisms of metastasis progression, thus providing potential additional therapeutic opportunities for treatment of lethal prostate cancer.

PMID:
30518758
PMCID:
PMC6281610
DOI:
10.1038/s41467-018-07511-4
[Indexed for MEDLINE]
Free PMC Article

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