How dietary fat influences cancer behavior has been a long-standing question in cancer biology and metabolism research. While obesity is recognized as a cancer risk factor, the molecular links between diet, lipid metabolism and tumor aggressiveness remain elusive. A recent study published in Cancer Research by Drs. Jiaqing Hao and Bing Li in the Department of Pathology at University of Iowa provides fresh insight into how specific dietary fats shape triple-negative breast cancer (TNBC) behavior. 

Using murine models of TNBC, the investigators compared two high-fat diets (HFD): olive oil HFD (rich in monounsaturated fatty acids) and cocoa butter HFD (rich in saturated fatty acids), alongside a low-fat diet as a control. Both HFD caused comparable obesity, but neither altered immune cell composition nor primary tumor growth. Strikingly, the olive oil HFD uniquely promoted metastasis. Mechanistic experiments revealed that this effect is mediated through the fatty acid–binding protein 5 (FABP5), which facilitates oleic-acid incorporation into cellular membranes and activates the PKC/ALDH signaling axis. Further analyses of human TNBC samples and public datasets confirmed that elevated FABP5 expression is associated with advanced disease and poor prognosis.

This study highlights that the type of dietary fat, but not obesity itself, may influence cancer progression, underscoring the importance of dietary composition in women with TNBC. These findings also provide a conceptual framework for personalized nutritional and therapeutic strategies targeting FABP5-mediated lipid signaling in breast cancer.

The work was supported by the National Cancer Institute’s Metabolic Dysregulation and Cancer Risk (MeDOC) Program and led by PhD candidate Anthony Avellino, with collaborations from Drs. Ingrid Lizarraga and Sonia Sugg (Department of Surgery) and Dr. Yi Huang (Department of Internal Medicine).

Read the full study here.