A hopeful new direction in the fight against breast cancer may lie in the body’s own defenses, as mouse experiments suggest that protection weakened by obesity could be restored.
Breast cancer develops in tissue surrounded by fat cells, and those cells may play a greater role in controlling tumor growth than previously understood. Researchers have discovered that fat cells in lean breast tissue produce a molecule that helps destroy cancerous cells. In obesity, production of this protective molecule drops, potentially removing one of the body’s natural defenses against breast cancer.
The finding comes from researchers at Huntsman Cancer Institute at the University of Utah (the U), who identified a previously underappreciated way obesity may contribute to breast cancer. Rather than simply creating conditions that encourage cancer growth, obesity may also weaken a biological process that normally helps eliminate dangerous cells.
The research was led by Keren Hilgendorf, PhD, a Huntsman Cancer Institute investigator and assistant professor of biochemistry at the U, and first author Meghan Curtin, a doctoral candidate in molecular biology at the university. Their findings were published in the journal Science.
Lean fat cells promote cancer cell death
Much of the breast consists of fat cells called adipocytes. These cells become larger with obesity, changing the surrounding tissue environment in ways that can affect cancer cells. By studying preclinical models, including breast tissue from donors, the researchers identified a key difference between lean and obese adipocytes involving a fatty acid known as 9S-HODE.
Lean adipocytes produced substantially more 9S-HODE than obese adipocytes. This molecule helps promote ferroptosis, a form of cell death involving iron-dependent damage to cellular fats. Ferroptosis is one of the processes through which the body can eliminate old or damaged cells, including those that could become cancerous.
“We found that the lean adipocytes produce much more 9S-HODE than obese ones. This means that cancerous cells die more readily in lean tissue,” says Curtin. “By producing more 9S-HODE, our bodies are actively protecting us, under lean circumstances, in a way it cannot with obesity.”
Boosting 9S-HODE suppresses tumor growth in mice
The researchers also tested whether restoring this molecule could change tumor growth. In preclinical mouse models, increasing 9S-HODE levels in obese adipocytes suppressed breast cancer tumor growth. This suggests that the reduced production of 9S-HODE associated with obesity may contribute directly to the loss of a protective mechanism.
For Hilgendorf, the results offer a different way to understand the relationship between obesity and cancer.
“We uncovered the role of a molecule that normally appears in lean tissue that restrains breast cancer growth but is less present with obesity,” says Hilgendorf. “We know obesity is often a driver of breast cancer, and researchers in our field usually consider how obesity is promoting the disease. But we hadn’t really considered that obesity could also be the loss of something that naturally protects us.”
Could 9S-HODE become a cancer therapy?
That distinction could have implications for treatment. If 9S-HODE helps limit tumor growth, researchers may eventually be able to develop therapies that restore its protective activity. The mouse experiments provide early evidence supporting this possibility, although further research is needed to determine whether the approach could work in patients.
“From a clinical perspective, this discovery is incredibly empowering. Because 9S-HODE is naturally present in the body but is lost with obesity, we may be able to restore this protection by putting it back,” says Hilgendorf. “That could become a very feasible therapeutic approach to slow breast cancer growth.”
The researchers emphasize that obesity is only one of several factors contributing to breast cancer, which can also develop for unrelated reasons. Their findings suggest that 9S-HODE is produced primarily by fat cells in the breast, although fat cells elsewhere in the body may provide similar protection. Whether this mechanism operates in other tissues remains an open question.
“We believe this shift in the understanding of the roles of lean and obese adipocytes is the start of something. This is just one discovery, and it’s not the end of the road,” says Curtin. “This opened our eyes to new ways to think about science, and hopefully we can harness what our bodies are already doing to make progress against this disease.”
Reference: “Lean adipocyte oxylipin signaling restrains breast cancer through ferroptosis” by Meghan C. Curtin, Abigail E. Jackson, Mark D. Lee, Elisabeth A. Brown, J. Alan Maschek, David H. Lum, James E. Cox, Alana L. Welm and Keren I. Hilgendorf, 10 September 2026, Science.
DOI: 10.1126/science.aea4287
The critical research happening every day at Huntsman Cancer Institute is supported by the National Institutes of Health/National Cancer Institute, including cancer center support grant P30 CA042014, as well as Huntsman Cancer Foundation.
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