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An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
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An aberrant SREBP-dependent lipogenic program promotes metastatic prostate cancer
Ming Chen1, Jiangwen Zhang2, Katia Sampieri1,3
1Cancer Research Institute, Beth Israel Deaconess Cancer Center, Department of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Nature Genetics
|January 17, 2018
Summary
Loss of PML and PTEN in prostate cancer promotes metastasis by activating a SREBP lipogenic program. Targeting SREBP or reducing high-fat diet intake may inhibit cancer spread.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Lipids play a role in cancer development.
- PML and PTEN are frequently co-deleted in metastatic prostate cancer (CaP).
Purpose of the Study:
- Investigate the role of PML in prostate cancer metastasis.
- Elucidate the mechanisms linking lipid metabolism to prostate cancer progression.
Main Methods:
- Used a mouse model with conditional Pml inactivation in Pten-null prostate tumors.
- Analyzed tumor characteristics, lipid profiles, and gene expression.
- Administered fatostatin and high-fat diet (HFD) to evaluate therapeutic and dietary effects.
Main Results:
- Pml inactivation in Pten-null mice accelerated indolent tumors into lethal metastatic disease.
- Metastatic tumors exhibited MAPK reactivation and a hyperactivated SREBP prometastatic lipogenic program.
- Fatostatin treatment inhibited tumor growth and metastasis in vivo.
- HFD promoted lipid accumulation and metastasis in a nonmetastatic Pten-null CaP model.
Conclusions:
- PML loss cooperates with PTEN loss to drive prostate cancer metastasis via an SREBP-driven lipogenic program.
- Targeting SREBP or dietary fat intake represents potential therapeutic strategies against metastatic prostate cancer.
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