Related Experiment Video
Updated: May 14, 2026
09:43
Isolation, Culture, and Characterization of Prostate Cancer-Associated Fibroblasts
Published on: August 1, 2025
DGAT1 Drives Racially Divergent Fibroblast Activation via ERK1/2-Dependent Tumorigenic Signaling in Prostate Cancer
Sathyavathi ChallaSivaKanaka1, Mamatha Kakarla1, Renee E Vickman1,2
1Department of Surgery, NorthShore University HealthSystem, Evanston, Illinois.
Cancer Research Communications
|May 12, 2026
Summary
African American men face higher lethal prostate cancer (PCa) rates due to race-associated differences in lipid metabolism. Targeting DGAT1 in cancer-associated fibroblasts (CAFs) shows promise for reducing PCa disparities.
Area of Science:
- Oncology
- Cancer Biology
- Metabolic Reprogramming
Background:
- Lethal prostate cancer (PCa) disproportionately affects African American (AA) men, with disparities linked to race-associated lipid metabolic reprogramming.
- Carcinoma-associated fibroblasts (CAFs) are identified as key stromal cells mediating racial disparities in PCa progression.
Purpose of the Study:
- To investigate the role of lipid metabolism in racial disparities of prostate cancer.
- To determine the function of diacylglycerol O-acyltransferase 1 (DGAT1) in lipid accumulation within CAFs and its impact on tumor progression.
Main Methods:
- Analysis of lipid droplet (LD) biogenesis and storage in CAFs from AA and European American (EA) patients.
- Investigating the effect of DGAT1 expression and inhibition on fibroblast activation, secretome, and PCa cell growth.
- Integrative transcriptomic and secretome analyses to identify DGAT1-regulated genes and pathways.
Main Results:
- Lipid-laden CAFs from AA patients (AACAF) exhibit enhanced pro-tumorigenic properties compared to those from EA patients (EACAF).
- DGAT1 enzyme activity drives LD accumulation in AACAF, promoting fibroblast activation and altering the tumor microenvironment (TME).
- DGAT1 inhibition suppressed pro-tumorigenic pathways, including those involving BDNF, VEGF, and TSP1, with racially distinct regulation.
Conclusions:
- DGAT1 is a critical regulator of fibroblast activation and lipid-driven remodeling in the PCa TME of AA men.
- Targeting DGAT1 offers a potential strategy to disrupt metabolic-stromal crosstalk and mitigate race-associated disparities in PCa.
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