Researchers Uncover Link Between Omega 6 Fatty Acid and Aggressive Breast Cancer
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Linoleic acid, an omega-6 fatty acid enhanced the growth of the hard-to-treat “triple negative” breast cancer subtype, according to a preclinical study led by Weill Cornell Medicine investigators.
In the study, published in Science, the researchers found that linoleic acid can activate a major growth pathway in tumor cells by binding to a protein called FABP5. Comparing breast cancer subtypes, the team observed that this growth pathway activation occurs in triple-negative tumor cells, where FABP5 is particularly abundant, but not in other hormone-sensitive subtypes. In a mouse model of triple-negative breast cancer, a diet high in linoleic acid enhanced tumor growth.
Researchers looked at the ability of omega-6 fatty acids—particularly linoleic acid to drive an important, nutrient-sensing growth pathway called the mTORC1 pathway.
A key initial finding was that linoleic acid does indeed activate mTORC1 in cell and animal models of breast cancers, but only in triple-negative subtypes. The scientists discovered that this subtype-specific effect occurs because the polyunsaturated fatty acid forms a complex with FABP5, which is produced at high levels in triple-negative breast tumors but not in other subtypes, leading to the assembly and activation of mTORC1, a major regulator of cell metabolism and cancer cell growth.
Feeding mice that model triple-negative breast cancer a high-linoleic-acid diet increased FABP5 levels, mTORC1 activation and tumor growth. The researchers also found increased levels of FABP5 and linoleic acid in the tumors and blood samples from newly diagnosed triple-negative patients.
The illumination of FABP5’s importance in this process suggests, moreover, that it could be a good “biomarker” to guide more personalized nutritional and therapeutic interventions for patients with triple negative breast cancer, which currently lacks any targeted therapy.
Reference: Nikos Koundouros et al., Direct sensing of dietary ω-6 linoleic acid through FABP5-mTORC1 signaling.Science387,eadm9805(2025).DOI:10.1126/science.adm9805
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