Lipid Uptake Is an Androgen-Enhanced Lipid Supply Pathway Associated with Prostate Cancer Disease Progression and Bone Metastasis

Molecular Cancer Research : MCR
Kaylyn D TousignantMartin C Sadowski

Abstract

De novo lipogenesis is a well-described androgen receptor (AR)-regulated metabolic pathway that supports prostate cancer tumor growth by providing fuel, membrane material, and steroid hormone precursor. In contrast, our current understanding of lipid supply from uptake of exogenous lipids and its regulation by AR is limited, and exogenous lipids may play a much more significant role in prostate cancer and disease progression than previously thought. By applying advanced automated quantitative fluorescence microscopy, we provide the most comprehensive functional analysis of lipid uptake in cancer cells to date and demonstrate that treatment of AR-positive prostate cancer cell lines with androgens results in significantly increased cellular uptake of fatty acids, cholesterol, and low-density lipoprotein particles. Consistent with a direct, regulatory role of AR in this process, androgen-enhanced lipid uptake can be blocked by the AR-antagonist enzalutamide, but is independent of proliferation and cell-cycle progression. This work for the first time comprehensively delineates the lipid transporter landscape in prostate cancer cell lines and patient samples by analysis of transcriptomics and proteomics data, including the plasma me...Continue Reading

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Citations

May 31, 2019·International Journal of Molecular Sciences·Gergana E Stoykova, Isabel R Schlaepfer
May 1, 2020·American Journal of Men's Health·Hisashi HiranoShigeo Horie
Jan 26, 2021·Cellular Oncology (Dordrecht)·Clara LemosBernard Haendler
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Dec 9, 2020·Seminars in Cancer Biology·Claudia PeitzschAnna Dubrovska

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