An aberrant SREBP-dependent lipogenic program promotes metastatic prostate cancer.


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.





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Publication Info

Chen, Ming, Jiangwen Zhang, Katia Sampieri, John G Clohessy, Lourdes Mendez, Enrique Gonzalez-Billalabeitia, Xue-Song Liu, Yu-Ru Lee, et al. (2018). An aberrant SREBP-dependent lipogenic program promotes metastatic prostate cancer. Nature genetics, 50(2). pp. 206–218. 10.1038/s41588-017-0027-2 Retrieved from

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Ming Chen

Associate Professor in Pathology

Our laboratory is interested in understanding the molecular and genetic events underlying cancer progression and metastasis. The focus of our work is a series of genetically engineered mouse models that faithfully recapitulate human disease. Using a combination of mouse genetics, omics technologies, cross-species analyses and in vitro approaches, we aim to identify cancer cell–intrinsic and –extrinsic mechanisms driving metastatic cancer progression, with a long–term goal of developing new therapeutic strategies for preventing and treating metastatic disease. 

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