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Updated: Feb 13, 2026

An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Cholesterol Esterification Inhibition Suppresses Prostate Cancer Metastasis by Impairing the Wnt/β-catenin Pathway
Hyeon Jeong Lee1,2,3, Jie Li4, Renee E Vickman1,2
1Interdisciplinary Life Science Program, Purdue University, West Lafayette, Indiana.
Abstract:
Dysregulation of cholesterol is a common characteristic of human cancers including prostate cancer. This study observed an aberrant accumulation of cholesteryl ester in metastatic lesions using Raman spectroscopic analysis of lipid droplets in human prostate cancer patient tissues. Inhibition of cholesterol esterification in prostate cancer cells significantly suppresses the development and growth of metastatic cancer lesions in both orthotopic and intracardiac injection mouse models. Gene expression profiling reveals that cholesteryl ester depletion suppresses the metastatic potential through upregulation of multiple regulators that negatively impact metastasis. In addition, Wnt/β-catenin, a vital pathway for metastasis, is downregulated upon cholesteryl ester depletion. Mechanistically, inhibition of cholesterol esterification significantly blocks secretion of Wnt3a through reduction of monounsaturated fatty acid levels, which limits Wnt3a acylation. These results collectively validate cholesterol esterification as a novel metabolic target for treating metastatic prostate cancer. Mol Cancer Res; 16(6); 974-85. ©2018 AACR.
Insights
Inhibiting cholesterol esterification in prostate cancer cells suppresses metastasis. This metabolic pathway is a potential new target for treating advanced prostate cancer.
Area of Science:
- Oncology
- Metabolic pathways
- Cancer research
Background:
- Cholesterol dysregulation is common in human cancers, including prostate cancer.
- Aberrant accumulation of cholesteryl ester is observed in metastatic prostate cancer lesions.
Purpose of the Study:
- To investigate the role of cholesterol esterification in prostate cancer metastasis.
- To explore cholesterol esterification as a potential therapeutic target for metastatic prostate cancer.
Main Methods:
- Raman spectroscopic analysis of lipid droplets in patient tissues.
- Inhibition of cholesterol esterification in prostate cancer cells.
- Orthotopic and intracardiac injection mouse models for metastasis studies.
- Gene expression profiling to analyze metastatic potential regulators.
Main Results:
- Inhibition of cholesterol esterification suppressed the development and growth of metastatic lesions in mouse models.
- Cholesteryl ester depletion upregulated metastasis-inhibiting regulators and downregulated the Wnt/β-catenin pathway.
- Inhibition of cholesterol esterification blocked Wnt3a secretion by reducing monounsaturated fatty acid levels.
Conclusions:
- Cholesterol esterification is a novel metabolic target for treating metastatic prostate cancer.
- Targeting cholesterol metabolism offers a promising strategy for prostate cancer therapy.
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