| First Author | Chen M | Year | 2018 |
| Journal | Nat Genet | Volume | 50 |
| Issue | 2 | Pages | 206-218 |
| PubMed ID | 29335545 | Mgi Jnum | J:260988 |
| Mgi Id | MGI:6151963 | Doi | 10.1038/s41588-017-0027-2 |
| Citation | Chen M, et al. (2018) An aberrant SREBP-dependent lipogenic program promotes metastatic prostate cancer. Nat Genet 50(2):206-218 |
| abstractText | 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. |
