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.

Details

Title
NSD2 is a conserved driver of metastatic prostate cancer progression
Author
Aytes, Alvaro 1 ; Giacobbe, Arianna 2 ; Mitrofanova, Antonina 3 ; Ruggero, Katia 4 ; Cyrta, Joanna 5 ; Arriaga, Juan 2 ; Palomero, Luis 4 ; Farran-Matas, Sonia 4 ; Rubin, Mark A 6 ; Shen, Michael M 7   VIAFID ORCID Logo  ; Califano, Andrea 8 ; Abate-Shen, Cory 9 

1  Department of Urology, Columbia University Irving Medical Center, New York, NY, USA; 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, Barcelona, Spain 
2  Department of Urology, Columbia University Irving Medical Center, New York, NY, USA; Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA 
3  Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA; Department of Health Informatics, Rutgers School of Health Professions, Rutgers, The State University of New Jersey, Newark, NJ, USA 
4  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, Barcelona, Spain 
5  Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA 
6  Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA; Department for BioMedical Research, University of Bern, Bern, Switzerland 
7  Department of Urology, Columbia University Irving Medical Center, New York, NY, USA; Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA; Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA 
8  Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA; Department of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, New York, NY, USA 
9  Department of Urology, Columbia University Irving Medical Center, New York, NY, USA; Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA 
Pages
1-14
Publication year
2018
Publication date
Dec 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-07511-4
ProQuest document ID
2150519946
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.