NSD2 is a conserved driver of metastatic prostate cancer progression

• DOI: 10.1038/s41467-018-07511-4
• Publication Date: 2018-11-29T17:33:24Z
• Authors: Alvaro Aytes; Arianna Giacobbe; Antonina Mitrofanova; Katia Ruggero; Joanna Cyrta; Juan Arriaga; Luis Palomero; Sonia Farran-Matas; Mark A. Rubin; Michael M. Shen; Andrea Califano; Cory Abate-Shen
• Keywords: Male; 0303 health sciences; Science; Q; Mice, Nude; Prostatic Neoplasms; Histone-Lysine N-Methyltransferase; Article; 3. Good health; Gene Expression Regulation, Neoplastic; Repressor Proteins; Mice; 03 medical and health sciences; Cell Line, Tumor; Disease Progression; Animals; Humans; Gene Silencing; Neoplasm Metastasis; RNA, Small Interfering

AbstractDeciphering 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.