|Title||NSD2 is a conserved driver of metastatic prostate cancer progression.|
|Publication Type||Journal Article|
|Year of Publication||2018|
|Authors||Aytes 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|
|Date Published||2018 12 05|
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.
|Alternate Journal||Nat Commun|
|PubMed Central ID||PMC6281610|