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. Author manuscript; available in PMC: 2015 Mar 4.
Published in final edited form as: Cell Metab. 2014 Mar 4;19(3):393–406. doi: 10.1016/j.cmet.2014.01.019

Figure 7. Molecular pathways underlying accumulation of CE in advanced human PCa and suppression of cancer proliferation upon CE depletion.

Figure 7

The schematic shows that loss of PTEN activates PI3K/AKT/mTOR pathway, which in turn upregulates SREBP and LDLr. LDL is then hydrolyzed to free fatty acids and free cholesterol (FC) in lysosome. The excess FC together with the fatty acyl CoA substrate is converted to CE by ACAT-1 and stored in LDs. LDL also serves as an important carrier of ω-6 polyunsaturated fatty acid (PUFA), such as AA, which promotes cell proliferation and tumor growth. The red arrows depict the consequences of CE depletion. Depletion of CE storage by ACAT-1 knockdown or ACAT inhibition disturbs cholesterol homeostasis by elevating FC levels and consequently downregulating expression levels of SREBP and LDLr. Subsequently reduced uptake of ω-6 PUFA from LDL suppresses cancer proliferation.