NSD2 is a conserved driver of metastatic prostate cancer progression
| Autor: | Cory Abate-Shen, Alvaro Aytes, Antonina Mitrofanova, Luis Palomero, Joanna Cyrta, Andrea Califano, Katia Ruggero, Mark A. Rubin, Michael M. Shen, Juan Arriaga, Arianna Giacobbe, Sonia Farran-Matas |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Science General Physics and Astronomy Mice Nude General Biochemistry Genetics and Molecular Biology Article Metastasis 03 medical and health sciences Prostate cancer Mice In vivo Cell Line Tumor medicine Gene silencing Animals Humans Gene Silencing Neoplasm Metastasis RNA Small Interfering lcsh:Science Regulation of gene expression Multidisciplinary business.industry Cancer Prostatic Neoplasms General Chemistry Histone-Lysine N-Methyltransferase medicine.disease 3. Good health Gene expression profiling Gene Expression Regulation Neoplastic Repressor Proteins 030104 developmental biology Genetically Engineered Mouse Cancer research Disease Progression lcsh:Q business |
| Zdroj: | Nature Communications Nature Communications, Vol 9, Iss 1, Pp 1-14 (2018) |
| ISSN: | 2041-1723 |
| Popis: | 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. Identifying cell intrinsic mechanisms promoting metastasis are necessary to develop new cancer therapeutics. Here they do cross-species computational analysis and identify nuclear receptor binding SET domain Protein 2 (NSD2) as a driver of prostate cancer metastasis. |
| Databáze: | OpenAIRE |
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