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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.identifier 10.1038/s41588-017-0027-2
dc.identifier.issn 1061-4036
dc.identifier.issn 1546-1718
dc.identifier.uri https://hdl.handle.net/10161/20378
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.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.id Chen, Ming|0914251
dc.date.updated 2020-04-06T05:41:42Z
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
duke.contributor.orcid Chen, Ming|0000-0002-3470-1062


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