International Business Department           Liu Bojia           March 17, 2025

  A growing body of research evidence suggests that diet has an important impact on disease progression and treatment outcomes in cancer patients. This is because specific nutrients, in excess or deficiency, may affect cell growth and proliferation at the molecular level.

  A recent research paper published in the leading academic journal Science highlights the growth-promoting effects of linoleic acid, a fatty acid commonly found in the diet, on certain deadly tumours.

  Linoleic acid is a type of omega-6 polyunsaturated fatty acid, an essential fatty acid that is obtained through the diet. Many vegetable oils (e.g., sunflower oil, soybean oil, peanut oil, etc.) are rich in linoleic acid, and nuts (e.g., walnuts, pine nuts), beef and lamb also contain a lot of linoleic acid. Unlike omega-3, which is also a polyunsaturated fatty acid, and which is recognised as a healthy fatty acid and is beneficial for the prevention of cancer, inflammation, cardiovascular disease, etc., the health effects of omega-6 fatty acids are quite controversial. On the one hand, omega-6 fatty acids are thought to have a beneficial effect on cholesterol levels; on the other hand, omega-6 fatty acids are also thought to promote mild inflammation because they are converted in the body to arachidonic acid, which in turn synthesises prostaglandins, among other things, that mediate inflammatory responses.

  It is worth noting, however, that many people tend to overdose on omega-6 fatty acids and underdose on omega-3 fatty acids in their daily diets, especially in Western diets that are high in processed foods.

  In this Science study, researchers at Weill Cornell Medical College analysed how different types of breast cancer cells perceive and utilise omega-6 linoleic acid as a nutrient.

  The intracellular rapamycin target protein complex, mTORC1, is an important regulator of cellular nutrients, integrating extracellular nutritional cues with intracellular anabolic processes to regulate cell growth. The study authors first found that the mTORC1 pathway can be activated by omega-6 linoleic acid, but not directly by omega-3 fatty acids.

  Further along the mTORC1 pathway, the researchers found that the activation of mTORC1 by omega-6 linoleic acid had a characteristic: it depended on a fatty acid-binding protein called FABP5. FABP5 prompts the interaction of linoleic acid with the mTORC1 complex, regulating substrate binding, localisation within the cell, etc., and ultimately regulating protein synthesis. Some other lipids (e.g., oleic acid, palmitic acid, etc.) have also been found to activate mTORC1, but the process does not require FABP5.

  However, precisely in the most difficult to treat and deadliest subtype of breast cancer, triple-negative breast cancer (i.e., negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor HER2), the authors found that the amount of FABP5 in cancer cells was higher than in any other type of cell. This means that in triple-negative breast cancer cells with high FABP5 expression, omega-6 linoleic acid ingested through the diet is likely to sufficiently activate the mTORC pathway to stimulate cell growth.

  And the authors also proved this in a mouse model. They divided the mice into two groups and fed them with two sets of diets. Both sets of diets had the same other nutrients, the only difference being the polyunsaturated fatty acids, with one set using safflower seed oil (an oil commonly used in salad dressings and sauces), which is rich in omega-6 linoleic acid, and the other using flaxseed with fish oil, which is rich in omega-3 fatty acids. The researchers then implanted triple-negative breast cancer cells into the mammary glands of mice and observed the growth of the cancer cells. The results showed that the tumours grew significantly faster in the mice that consumed omega-6 linoleic acid. Consistent with this, mTORC1 signalling within the tumours was also stronger.

  The researchers concluded in their paper that these results both explain why different breast cancer subtypes respond differently to dietary fats and also reveal an interaction between linoleic acid intake and breast cancer. This study also further demonstrates the importance of nutritional interventions in cancer treatment, and given that omega-6 linoleic acid can only be obtained through the diet, restricting dietary linoleic acid intake could be part of the treatment strategy for triple-negative breast cancer with high FABP5.