Journal article
FABP4-mediated lipid accumulation and lipolysis in tumor-associated macrophages promote breast cancer metastasis
eLife, Vol.13, RP101221
11/08/2024
DOI: 10.7554/eLife.101221.2
Abstract
A high density of tumor-associated macrophages (TAMs) is associated with poorer prognosis and survival in breast cancer patients. Recent studies have shown that lipid accumulation in TAMs can promote tumor growth and metastasis in various models. However, the specific molecular mechanisms that drive lipid accumulation and tumor progression in TAMs remain largely unknown. Herein, we demonstrated that unsaturated fatty acids (FAs), unlike saturated ones, are more likely to form lipid droplets in murine macrophages. Specifically, unsaturated FAs, including linoleic acids (LA), activate the FABP4/CEBPα pathway, leading to triglyceride synthesis and lipid droplet formation. Furthermore, FABP4 enhances lipolysis and FA utilization by breast cancer cell lines, which promotes cancer cell migration in vitro and metastasis in vivo. Notably, a deficiency of FABP4 in murine macrophages significantly reduces LA-induced lipid metabolism. Therefore, our findings suggest FABP4 as a crucial lipid messenger that facilitates unsaturated FA-mediated lipid accumulation and lipolysis in TAMs, thus contributing to the metastasis of breast cancer.
Details
- Title: Subtitle
- FABP4-mediated lipid accumulation and lipolysis in tumor-associated macrophages promote breast cancer metastasis
- Creators
- Matthew Yorek - University of IowaXingshan Jiang - University of IowaShanshan Liu - University of IowaJiaqing Hao - University of IowaJianyu Yu - University of IowaAnthony Avellino - University of IowaZhanxu Liu - University of LouisvilleMelissa Curry - University of Iowa Hospitals and ClinicsHenry Keen - University of IowaJianqiang Shao - University of IowaAnand Kanagasabapathy - University of Iowa, PathologyMaying KongYiqin Xiong - University of IowaEdward R Sauter - Center for Cancer ResearchSonia L Sugg - University of Iowa, SurgeryBing Li - University of Iowa
- Resource Type
- Journal article
- Publication Details
- eLife, Vol.13, RP101221
- DOI
- 10.7554/eLife.101221.2
- ISSN
- 2050-084X
- eISSN
- 2050-084X
- Language
- English
- Date published
- 11/08/2024
- Academic Unit
- Pathology; Surgery; Iowa Institute of Human Genetics
- Record Identifier
- 9984746952902771
Metrics
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