High cholesterol fuels cancer, stimulating resistance to a form of cell death
Chronic high cholesterol levels are known to be associated with increased risk of breast cancer and poorer results in most cancers, but the link has not been fully understood so far.
In a study published online on August 24 in the journal Nature Communications , a research team led by the Duke Cancer Institute identified the mechanisms of action, describing how breast cancer cells use cholesterol to develop tolerance to stress, making them unassailable while migrating from the site of the original tumor.
“Most cancer cells die while trying to metastasize – it’s a very stressful process,” says author Donald P. McDonnell, Ph.D., a professor in the Department of Pharmacology, Biology and Cancer Medicine at Duke University School of Medicine. . “Few who do not die have this ability to overcome the stress-induced death cell mechanism. And cholesterol has been instrumental in fueling this ability. ”
McDonnell and colleagues relied on previous laboratory research and focused on the link between high cholesterol and estrogen-positive breast and gynecologic cancer. The results showed how estrogen-fed cancers benefited from cholesterol derivatives that act like estrogen, stimulating cancer growth.
But at the same time, a paradox has emerged for estrogen-negative breast and gynecological cancers. These cancers are not estrogen dependent, but high cholesterol is even in these conditions associated with a more serious disease, suggesting that there may be a different mechanism.
In the current study, using cancer cells and mouse models, researchers at Duke found that migratory cancer cells swallow cholesterol in response to stress. Most people die.
But in the philosophy of the proverb “What doesn’t kill you makes you stronger”, surviving people appear with a superpower that makes them able to resist ferroptosis, a natural process in which cells succumb to stress. These stress-resistant cancer cells proliferate and metastasize easily.
The process appears to be used not only by ER-negative breast cancer cells, but also by other types of tumors, including melanoma. And the identified mechanisms could be targeted by various therapies.
“Identifying this course of action has highlighted new approaches that could be useful for the treatment of advanced diseases,” said McDonnell. “There are contemporary therapies under development that inhibit the path I have described. These findings again highlight why lowering cholesterol – either by using medications or by changing your diet – is a good strategy for better health. ”
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