An aberrant SREBP-dependent lipogenic program promotes metastatic prostate cancer.
| dc.contributor.author | Chen, Ming | |
| dc.contributor.author | Zhang, Jiangwen | |
| dc.contributor.author | Sampieri, Katia | |
| dc.contributor.author | Clohessy, John G | |
| dc.contributor.author | Mendez, Lourdes | |
| dc.contributor.author | Gonzalez-Billalabeitia, Enrique | |
| dc.contributor.author | Liu, Xue-Song | |
| dc.contributor.author | Lee, Yu-Ru | |
| dc.contributor.author | Fung, Jacqueline | |
| dc.contributor.author | Katon, Jesse M | |
| dc.contributor.author | Menon, Archita Venugopal | |
| dc.contributor.author | Webster, Kaitlyn A | |
| dc.contributor.author | Ng, Christopher | |
| dc.contributor.author | Palumbieri, Maria Dilia | |
| dc.contributor.author | Diolombi, Moussa S | |
| dc.contributor.author | Breitkopf, Susanne B | |
| dc.contributor.author | Teruya-Feldstein, Julie | |
| dc.contributor.author | Signoretti, Sabina | |
| dc.contributor.author | Bronson, Roderick T | |
| dc.contributor.author | Asara, John M | |
| dc.contributor.author | Castillo-Martin, Mireia | |
| dc.contributor.author | Cordon-Cardo, Carlos | |
| dc.contributor.author | Pandolfi, Pier Paolo | |
| dc.date.accessioned | 2020-04-06T05:41:44Z | |
| dc.date.available | 2020-04-06T05:41:44Z | |
| dc.date.issued | 2018-02 | |
| dc.date.updated | 2020-04-06T05:41:42Z | |
| dc.description.abstract | Lipids, either endogenously synthesized or exogenous, have been linked to human cancer. Here we found that PML is frequently co-deleted with PTEN in metastatic human prostate cancer (CaP). We demonstrated that conditional inactivation of Pml in the mouse prostate morphs indolent Pten-null tumors into lethal metastatic disease. We identified MAPK reactivation, subsequent hyperactivation of an aberrant SREBP prometastatic lipogenic program, and a distinctive lipidomic profile as key characteristic features of metastatic Pml and Pten double-null CaP. Furthermore, targeting SREBP in vivo by fatostatin blocked both tumor growth and distant metastasis. Importantly, a high-fat diet (HFD) induced lipid accumulation in prostate tumors and was sufficient to drive metastasis in a nonmetastatic Pten-null mouse model of CaP, and an SREBP signature was highly enriched in metastatic human CaP. Thus, our findings uncover a prometastatic lipogenic program and lend direct genetic and experimental support to the notion that a Western HFD can promote metastasis. | |
| dc.identifier | 10.1038/s41588-017-0027-2 | |
| dc.identifier.issn | 1061-4036 | |
| dc.identifier.issn | 1546-1718 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | Springer Science and Business Media LLC | |
| dc.relation.ispartof | Nature genetics | |
| dc.relation.isversionof | 10.1038/s41588-017-0027-2 | |
| dc.subject | Cell Line, Tumor | |
| dc.subject | Animals | |
| dc.subject | Mice, Inbred C57BL | |
| dc.subject | Mice, Knockout | |
| dc.subject | Humans | |
| dc.subject | Mice | |
| dc.subject | Prostatic Neoplasms | |
| dc.subject | Cell Transformation, Neoplastic | |
| dc.subject | Neoplasm Metastasis | |
| dc.subject | Cell Proliferation | |
| dc.subject | Male | |
| dc.subject | Lipogenesis | |
| dc.subject | PTEN Phosphohydrolase | |
| dc.subject | Sterol Regulatory Element Binding Proteins | |
| dc.subject | Metabolic Networks and Pathways | |
| dc.subject | PC-3 Cells | |
| dc.title | An aberrant SREBP-dependent lipogenic program promotes metastatic prostate cancer. | |
| dc.type | Journal article | |
| duke.contributor.orcid | Chen, Ming|0000-0002-3470-1062 | |
| pubs.begin-page | 206 | |
| pubs.end-page | 218 | |
| pubs.issue | 2 | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | Duke Cancer Institute | |
| pubs.organisational-group | Pathology | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | Institutes and Centers | |
| pubs.organisational-group | Clinical Science Departments | |
| pubs.publication-status | Published | |
| pubs.volume | 50 |