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In a nutshell
Researchers discovered that omega-6 fatty acids (common in vegetable oils and processed foods) can fuel triple-negative breast cancer growth through a protein called FABP5, while not affecting other breast cancer types.
In animal studies, mice fed diets high in omega-6 developed faster-growing tumors than those on omega-3-rich diets, suggesting dietary fat balance may influence cancer progression.
This pathway could lead to new treatments targeting FABP5 and might explain why some breast cancers respond differently to dietary factors, though researchers caution against making dramatic dietary changes based solely on this research.
NEW YORK — Research from Weill Cornell Medicine has identified a molecular pathway linking omega-6 linoleic acid—a common dietary fat in Western diets—to the growth of triple-negative breast cancer. This discovery helps explain why different breast cancer types respond differently to dietary patterns and points to potential new treatment approaches.
Triple-negative breast cancer lacks receptors for estrogen, progesterone, and HER2 protein, making it difficult to treat with hormone therapies or targeted drugs that work for other breast cancer types. This aggressive cancer accounts for about 15% of all breast cancers and currently has limited treatment options.
The Hidden Link Between Diet and Cancer
In the study published in the journal Science, researchers found that only triple-negative breast cancer cells showed increased activation of mTORC1—the cell’s master growth regulator—when exposed to omega-6 linoleic acid. Hormone receptor-positive breast cancer cells remained unaffected
Omega-6 linoleic acid is essential for human health but must be obtained through diet. It’s particularly abundant in processed foods, vegetable oils (especially safflower oil), and animal products. The typical Western diet contains far more omega-6 than omega-3 fatty acids, which may have health implications beyond what was previously understood.
The key factor appears to be a protein called FABP5 (fatty acid-binding protein 5), which was found at much higher levels in triple-negative breast cancer. When omega-6 linoleic acid enters a cancer cell, FABP5 attaches to it and then interacts with mTORC1, ultimately leading to increased cancer cell growth.
Vegetable oils have high levels of omega-6 lineolic acid, which is also found in abundance in many processed foods. (Photo by Unsplash+ in collaboration with Getty Images)
FABP5 and Omega-6 Fatty Acids
To verify their findings, researchers conducted experiments with mice fed different diets. One group received food high in omega-6 (safflower oil), while another group ate food rich in omega-3 (flaxseed and fish oils). The results were striking: mice on the omega-6-rich diet developed significantly faster-growing tumors.
The research team also examined blood samples from breast cancer patients. Both FABP5 and omega-6 fatty acids were higher in the serum of triple-negative breast cancer patients (albeit from a small patient sample) compared to those with hormone receptor-positive disease.
Another interesting finding was that cancer cells can release FABP5 into their surroundings, potentially influencing nearby cells that normally have low FABP5 levels. This suggests that cancer cells might create a favorable environment for continued growth.
More Research Ahead
This research has important implications for both cancer prevention and treatment. FABP5 could serve as a biomarker to identify patients who might benefit from dietary modifications or targeted therapies. Adjusting the balance of omega-6 to omega-3 fatty acids might complement existing treatments for certain patients.
The most promising aspect is the potential for new treatment approaches. Drugs that block the interaction between FABP5 and mTORC1 could potentially prevent dietary omega-6 fatty acids from fueling cancer growth. The researchers demonstrated this concept by creating a modified form of FABP5 that couldn’t interact with the mTORC1 pathway.
“There may be a broader role for FABP5-mTORC1 signaling in other cancer types and even in common chronic diseases such as obesity and diabetes,” says study first author Dr. Nikos Koundouros, a postdoctoral research associate at Weill Cornell, in a statement.
However, the researchers caution against making dramatic dietary changes based solely on this research. Their findings are most relevant to patients already diagnosed with triple-negative breast cancer, particularly those with high FABP5 levels. Before adjusting your diet, you should always consult your physician first.
This study provides a mechanistic explanation for the long-suspected relationship between dietary fats and breast cancer. It highlights that cancer is not just influenced by genetics but also by metabolism and diet—what’s on our plates may affect what happens in our cells.
Points for Consideration
Before interpreting the findings of this study, readers should bear in mind several important limitations and points of contention:
Limited Human Evidence
The study’s conclusions regarding FABP5 and omega-6 fatty acids in breast cancer patients are drawn from a small sample size (only 6 triple-negative and 18 hormone receptor-positive patients). Larger clinical studies are necessary to confirm these observations.
Laboratory vs. Real-world Conditions
The experiments primarily used cell lines and mouse models. These controlled conditions do not fully replicate the complex biology and interactions that occur within human tumors and their environments.
Complexity of Cancer Biology
While the study highlights the FABP5-mTORC1 pathway as significant, cancer involves many interacting pathways. Other genetic or environmental factors not explored in this research might also significantly impact disease progression.
Dietary Implications
The researchers caution against making immediate or dramatic dietary changes based on these results alone. The findings are specifically relevant to individuals already diagnosed with triple-negative breast cancer, particularly those showing high FABP5 levels.
Potential Conflicts of Interest
Several researchers involved in this study have founded a company seeking to develop therapies targeting the FABP5-mTORC1 pathway. While common in scientific research, readers should be aware of these interests.
Considering these factors will help ensure a balanced interpretation of the study’s implications.
Paper Summary
Methodology
The researchers conducted a comprehensive investigation using multiple approaches. They first tested how different fatty acids affected cellular signaling in various breast cancer cell lines representing the main clinical subtypes: estrogen receptor-positive, HER2-positive, and triple-negative. After treating these cells with either omega-6 linoleic acid or omega-3 alpha-linolenic acid, they measured activation of various signaling pathways, focusing on mTORC1.
When they observed that only triple-negative cells responded to omega-6 linoleic acid, they analyzed genetic data from the METABRIC study (with 1,904 tumor samples) and found FABP5 was significantly overexpressed in triple-negative versus receptor-positive breast cancers.
To understand how FABP5 and omega-6 linoleic acid interacted, they conducted detailed molecular studies including protein binding assays and microscopy to visualize where these proteins localized within cells. They also performed experiments where they either reduced FABP5 in triple-negative cells or introduced it into hormone receptor-positive cells to confirm its role.
For animal studies, they used immunodeficient mice fed diets either enriched with safflower oil (high in omega-6) or flaxseed and fish oils (high in omega-3). These mice were then injected with triple-negative breast cancer cells to monitor tumor growth over time. The team also collected blood samples from newly diagnosed breast cancer patients and analyzed patient-derived tumor samples to validate their findings in human tissues.
Results
The laboratory experiments showed that omega-6 linoleic acid increased mTORC1 activity 2-3 fold in triple-negative breast cancer cells but had no effect on hormone receptor-positive cells. When FABP5 was removed using genetic techniques, the cancer cells no longer responded to omega-6 linoleic acid, confirming its essential role. Conversely, when FABP5 was added to hormone receptor-positive cells, they gained the ability to respond to omega-6 linoleic acid.
Detailed protein studies revealed that FABP5 binds directly to a component of mTORC1 called Raptor through a specific protein region, enhancing complex formation and downstream signaling. In mice, those fed the omega-6-rich diet showed approximately 3-fold faster tumor growth compared to those on an omega-3-rich diet. Tumors from the omega-6 group also showed higher levels of activated mTORC1 signaling.
Analysis of patient samples revealed that FABP5 protein levels were approximately 10-fold higher in triple-negative breast cancer patients compared to those with hormone receptor-positive disease. Similarly, omega-6 fatty acid levels were about 3-fold higher in triple-negative patients.
The researchers also found that cancer cells can secrete FABP5 into their environment. When normal breast cells were exposed to this secreted FABP5 along with omega-6 linoleic acid, they showed increased mTORC1 activation and proliferation, suggesting a mechanism for cancer cells to influence their surroundings.
Limitations
While the results are compelling, this research has some limitations. The study relied heavily on laboratory cell lines and mouse models, which may not fully represent the complexity of human breast cancer. The patient sample size for blood analysis was relatively small, with only 6 triple-negative breast cancer patients compared to 18 hormone receptor-positive patients.
The mouse studies used artificial conditions—immunodeficient mice with human cancer cell transplants—which may not perfectly mirror how tumors naturally develop in humans. Additionally, while the study focused on one mechanism linking FABP5 to mTORC1, cancer biology involves multiple interacting pathways that weren’t fully explored.
Furthermore, while the study showed associations between FABP5 levels, omega-6 fatty acids, and triple-negative breast cancer, it doesn’t prove that dietary modifications alone would significantly change outcomes in patients. The researchers also didn’t investigate genetic factors that might influence FABP5 expression or function, or how other dietary components might interact with this pathway.
Research Funding and Disclosures
This research was supported by National Institutes of Health grants R01GM051405 and R01CA046595 to John Blenis, and a Charles H. Revson Senior Fellowship in Biomedical Science (grant no. 23-23) to Nikos Koundouros. The team also acknowledged donations from the Joseph M. Simmons Foundation for ongoing lipid-focused research.
It’s worth noting that lead researchers Nikos Koundouros and John Blenis, along with researcher Zhongchi Li, disclosed that they are cofounders of Elikia, Inc., and are seeking to file patents related to therapeutic interventions targeting the FABP5-mTORC1 pathway based on their findings. This represents a common pathway for translating basic research discoveries into potential clinical applications.
About the Publication
The study, “Direct sensing of dietary ω-6 linoleic acid through FABP5-mTORC1 signaling,” was published in Science (Volume 387, eadm9805) on March 14, 2025. The research was conducted by a team led by Nikos Koundouros and John Blenis from Weill Cornell Medicine, with contributions from researchers across multiple departments including Pharmacology, Neurology, Medicine, and Biochemistry. The paper underwent peer review before acceptance on January 14, 2025, following initial submission in November 2023 and resubmission in October 2024.