Cholesteryl Ester Accumulation Induced by PTEN Loss and PI3K/AKT Activation Underlies Human Prostate Cancer Aggressiveness
By Shuhua Yue, Junjie Li, Seung-Young Lee, Hyeon Jeong Lee, Tiansong Shao, B. Song, Liang Cheng, T. Masterson, Xiaoqi Liu, T. Ratliff and 1 more. Cell Metabolism, 2014
828 citations recorded by the source corpus.
Summary Altered lipid metabolism is increasingly recognized as a signature of cancer cells. Enabled by label-free Raman spectromicroscopy, we performed quantitative analysis of lipogenesis at single cell level in human patient cancerous tissues. Our imaging data revealed an unexpected, aberrant accumulation of esterified cholesterol in lipid droplets of high-grade prostate cancer and metastases. Biochemical study showed that such cholesteryl ester accumulation was a consequence of loss of tumor suppressor PTEN and subsequent activation of PI3K/AKT pathway in prostate cancer cells. Furthermore, we found that such accumulation arose from significantly enhanced uptake of exogenous lipoproteins and required cholesterol esterification. Depletion of cholesteryl ester storage significantly reduced cancer proliferation, impaired cancer invasion capability, and suppressed tumor growth in mouse xenograft models with negligible toxicity. These findings open opportunities for diagnosing and treating prostate cancer by targeting the altered cholesterol metabolism.
Subfields: Biochemistry, Cancer Research, Surgery
View Paper: https://www.semanticscholar.org/paper/e9d9f37fe7af3e80d3d3126614659214087f791e
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Citations in the corpus
- Vibrational spectroscopic imaging of living systems: An emerging platform for biology and medicine (2015, methodology): “reported that lipid droplets in human patient prostate cancer cells are rich in cholesteryl ester (110).”