Researcher Uncovers How Dietary Fat May Fuel Cancer Growth

Estela Jacinto, a professor of biochemistry and molecular biology at Rutgers Robert Wood Johnson Medical School, has been studying a crucial pathway for human cell growth and metabolism for more than two decades.

So, when researchers figured out how certain cancers allow fats to hijack that pathway and grow uncontrollably, Jacinto was a natural person to explain that discovery’s importance for the journal Science.

She discusses the breakthrough.

What's the key discovery, and why is it important?
Researchers discovered that an essential fatty acid called omega-6 linoleic acid, which we can only get by eating it, directly activates a central growth pathway in our cells called mTORC1. This activation depends on a protein called FABP5, which acts as a lipid chaperone. When omega-6 linoleic acid binds to FABP5, it activates mTORC1, which then drives cell growth and proliferation.

This is significant because it links a specific dietary fat directly to the cellular machinery that controls growth, including the growth of cancer cells.

Why is it important to understand how dietary fats affect cell growth?
Dietary nutrients supply essential raw materials for cell growth and proliferation. Although a balanced diet promotes health, excess carbohydrates and fats can disrupt cellular processes, increasing the risk of diseases such as cancer.

Understanding how specific nutrients affect the cell growth machinery at the molecular level is vital to understanding the impacts of nutrition on human health.

What's the difference between omega-6 and omega-3 fatty acids, and why does it matter?
Both omega-6 linoleic acid and omega-3 linolenic acid are essential fatty acids, meaning our bodies can’t make them. We must obtain them through diet. Omega-6 is more abundant in the Western diet from vegetable oils, while omega-3 comes from sources like fish and nuts.

The research shows that omega-6, but not omega-3 or its derivatives, activates the mTORC1 growth pathway. This strengthens the notion that excess omega-6 can potentially have adverse effects by overstimulating mTORC1 and, consequently, deregulating cell growth.

How does this research link to cancer, particularly breast cancer?
The research found that FABP5, the lipid chaperone that enables omega-6 to activate mTORC1, is present in higher amounts in certain cancer types, especially triple-negative breast cancer, than in receptor-positive breast cancer.

When mice with implanted triple-negative breast cancer cells were fed diets with different fatty acids, those receiving omega-6 showed increased tumor growth, while those receiving omega-3 did not. This suggests that tumors with abundant FABP5 may preferentially use dietary omega-6 to fuel their growth.

What are the potential implications for cancer patients?
Since omega-6 is only obtained through diet, restricting its intake could benefit patients with high amounts of FABP5. The research points to a possible therapeutic strategy that combines targeting both mTOR and FABP5, along with dietary omega-6 restriction, for cancers that depend on the omega-6-FABP5-mTORC1 pathway. This approach could be particularly relevant for triple-negative breast cancer, which is a more aggressive form of breast cancer with limited treatment options.

How might this research influence dietary recommendations?
A balanced intake of omega-6 and omega-3 fatty acids is already gaining traction in promoting healthy immunity. This research adds another consideration, especially for cancer prevention and management.

Future studies should explore how manipulating the amounts of these lipids affects growth signals in different cell types, including immune cells, to potentially prevent cancer. But it's important to note that omega-6 is an essential fatty acid – we need some of it – so the goal would be balance rather than complete elimination.

What are the next steps for this research?
Targeting FABPs to treat cancer is currently under investigation, as are numerous clinical efforts targeting mTOR. However, mTOR inhibition alone has shown only modest results due to toxicity issues.

The new understanding of how omega-6 FABP5, and mTORC1 work together opens possibilities for more targeted approaches. Future research should investigate how excess dietary fat reprograms both cellular and whole-body metabolism, which could provide valuable insights into the mechanisms underlying cancer initiation and progression.

Why is this discovery particularly important for understanding cancer metabolism?
This research helps address a significant knowledge gap in how specific nutrients, particularly lipids, affect cell growth. It provides a step-by-step understanding of how a common dietary fat can fuel cancer proliferation.

By identifying the molecular players involved – omega-6 linoleic acid, FABP5 and mTORC1 – researchers now have new targets for potential therapeutic intervention. This could eventually lead to more personalized cancer treatments that consider both drug therapies and dietary modifications.