Journal article
An Olive Oil-Based High-Fat Diet Promotes Obesity-Driven Metastasis of Triple-Negative Breast Cancer
Cancer research (Chicago, Ill.), Vol.85(24), pp.5015-5032
12/15/2025
DOI: 10.1158/0008-5472.CAN-25-0822
PMCID: PMC12502211
PMID: 40911782
Abstract
Obesity is strongly associated with triple-negative breast cancer (TNBC). A better understanding of the molecular mechanisms driving obesity-induced TNBC progression could facilitate development of precision dietary intervention strategies. Here, we used murine models of obesity induced by different high-fat diets (HFDs) to examine their impact on TNBC progression. Compared to a low-fat diet (LFD), both cocoa butter and olive oil HFD induced similar levels of obesity. However, only the olive oil HFD-induced obesity increased TNBC stemness and lung metastasis. Mechanistically, oleic acid (OA) in the olive oil HFD facilitated TNBC metastasis by activating the protein kinase C (PKC)-aldehyde dehydrogenase (ALDH) pathway. Furthermore, fatty acid-binding protein 5 (FABP5) in TNBC cells was identified as essential for OA-mediated PKC/ALDH pathway activation. FABP5 deficiency reduced TNBC metastasis in multiple mouse models, whereas higher FABP5 expression correlated with worse outcomes of TNBC in various human studies. These findings collectively suggest that consumption of olive oil HFD promotes obesity-associated TNBC metastasis through OA/FABP5-driven oncogenic signaling.Obesity is strongly associated with triple-negative breast cancer (TNBC). A better understanding of the molecular mechanisms driving obesity-induced TNBC progression could facilitate development of precision dietary intervention strategies. Here, we used murine models of obesity induced by different high-fat diets (HFDs) to examine their impact on TNBC progression. Compared to a low-fat diet (LFD), both cocoa butter and olive oil HFD induced similar levels of obesity. However, only the olive oil HFD-induced obesity increased TNBC stemness and lung metastasis. Mechanistically, oleic acid (OA) in the olive oil HFD facilitated TNBC metastasis by activating the protein kinase C (PKC)-aldehyde dehydrogenase (ALDH) pathway. Furthermore, fatty acid-binding protein 5 (FABP5) in TNBC cells was identified as essential for OA-mediated PKC/ALDH pathway activation. FABP5 deficiency reduced TNBC metastasis in multiple mouse models, whereas higher FABP5 expression correlated with worse outcomes of TNBC in various human studies. These findings collectively suggest that consumption of olive oil HFD promotes obesity-associated TNBC metastasis through OA/FABP5-driven oncogenic signaling.
Details
- Title: Subtitle
- An Olive Oil-Based High-Fat Diet Promotes Obesity-Driven Metastasis of Triple-Negative Breast Cancer
- Creators
- Anthony Avellino - University of IowaXingshan Jiang - University of IowaMichael Lee - Yale UniversityJianyu Yu - University of IowaShanshan Liu - University of IowaXiaochun Han - University of IowaJerry Li - University of IowaJonathan Shilyansky - University of IowaZhaohua WangMelissa Curry - University of IowaYiqin Xiong - University of IowaIngrid M Lizarraga - University of IowaYi Huang - University of IowaSonia L Sugg - University of IowaJiaqing Hao - University of IowaBing Li - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.85(24), pp.5015-5032
- DOI
- 10.1158/0008-5472.CAN-25-0822
- PMID
- 40911782
- PMCID
- PMC12502211
- NLM abbreviation
- Cancer Res
- ISSN
- 1538-7445
- eISSN
- 1538-7445
- Publisher
- AMER ASSOC CANCER RESEARCH
- Grant note
- National Cancer Institute (NCI): R01CA180986, U01CA272424 National Institute of Allergy and Infectious Diseases (NIAID): R01AI137324
We thank the Biospecimen Procurement and Molecular Epidemiology Resource in the Holden Comprehensive Cancer Center for providing human samples, which are supported by the NCI under award P30CA086862. We thank the Department of Pathology at the University of Iowa for granting access to the Cytek Aurora flow cytometer. B. Li thanks the funding support from the NIH grants R01AI137324, R01CA180986, and U01CA272424 (part of the MeDOC Consortium).
- Language
- English
- Electronic publication date
- 09/05/2025
- Date published
- 12/15/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Surgery; Internal Medicine
- Record Identifier
- 9984958610102771
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