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SPORE in Prostate Cancer

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NSD2 is a conserved driver of metastatic prostate cancer progression.

TitleNSD2 is a conserved driver of metastatic prostate cancer progression.
Publication TypeJournal Article
Year of Publication2018
AuthorsAytes A, Giacobbe A, Mitrofanova A, Ruggero K, Cyrta J, Arriaga J, Palomero L, Farran-Matas S, Rubin MA, Shen MM, Califano A, Abate-Shen C
JournalNat Commun
Volume9
Issue1
Pagination5201
Date Published2018 12 05
ISSN2041-1723
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.

DOI10.1038/s41467-018-07511-4
Alternate JournalNat Commun
PubMed ID30518758
PubMed Central IDPMC6281610