Omega-6 Fat Linked to Aggressive Breast Cancer Growth: Study Uncovers Mechanism Behind Dietary Risk
A preclinical study led by researchers at Weill Cornell Medicine has revealed that linoleic acid—a common omega-6 fatty acid found in seed oils like soybean and safflower oil, as well as in animal products such as pork and eggs—can fuel the growth of the aggressive “triple-negative” breast cancer (TNBC) subtype. The findings, published on March 14 in Science, may pave the way for new dietary guidelines and targeted treatments for hard-to-treat cancers.
The research team discovered that linoleic acid activates a key tumor growth pathway, known as mTORC1, by binding to a protein called FABP5. This activation occurs specifically in triple-negative breast cancer cells, which produce high levels of FABP5, but not in hormone-sensitive breast cancer subtypes. In a mouse model of TNBC, a diet rich in linoleic acid led to faster tumor growth.
“This discovery helps clarify the relationship between dietary fats and cancer,” said senior author Dr. John Blenis, the Anna-Maria and Stephen Kellen Professor of Cancer Research at Weill Cornell Medicine. “It also opens up the potential for personalized nutrition strategies in cancer care.”
Linoleic acid is considered essential for health, but its consumption has surged since the 1950s due to the rise of seed oils in processed foods—especially in Western diets. While prior studies have hinted at possible links between omega-6 fats and disease, they lacked concrete biological explanations. This new study is the first to establish a clear mechanism linking linoleic acid to cancer growth.
The team focused on the role of the nutrient-sensing mTORC1 pathway in breast cancer progression. They found that linoleic acid uniquely activates this pathway in TNBC by forming a complex with FABP5, which is unusually abundant in this cancer subtype. This complex triggers mTORC1, a central regulator of cell growth and metabolism, thereby promoting tumor development.
Mice fed a high-linoleic-acid diet showed increased FABP5 expression, heightened mTORC1 activity, and more aggressive tumor growth. Additionally, elevated levels of both linoleic acid and FABP5 were found in blood and tumor samples from newly diagnosed TNBC patients.
These findings suggest that linoleic acid may influence breast cancer in a more precise way than previously thought. Importantly, the identification of FABP5 as a key player could make it a promising biomarker for guiding personalized treatment and nutritional approaches for TNBC patients—who currently have limited options for targeted therapy.
The researchers also observed similar mTORC1 activation in some prostate cancer subtypes and are now exploring whether this pathway plays a role in other cancers and metabolic diseases like obesity and diabetes.
“There may be a broader role for FABP5-mTORC1 signaling in other cancer types and even in common chronic diseases,” said lead author Dr. Nikos Koundouros, a postdoctoral researcher in the Blenis lab.
