DURHAM, N.C. — High cholesterol is a problem which most people typically associate with heart disease. Despite the condition’s obvious link to clogging arteries, studies show high cholesterol also plays a role in making cancer even more dangerous. Now, researchers from Duke University have discovered that having high cholesterol actually fuels cancer cells and can make them impervious to the natural stressors which usually kill them.
The new study finds that breast cancer cells use cholesterol to develop a tolerance to stress. This makes disease cells capable of withstanding the pressure of migrating from the cancerous tumor to other regions of the body.
“Most cancer cells die as they try to metastasize — it’s a very stressful process,” explains senior author Donald P. McDonnell, Ph.D., a professor in the departments of Pharmacology and Cancer Biology and Medicine, in a media release. “The few that don’t die have this ability to overcome the cell’s stress-induced death mechanism. We found that cholesterol was integral in fueling this ability.”
How high cholesterol gives cancer cells a ‘superpower’
McDonnell and his team followed up on previous studies from their lab that examined the link between high cholesterol and estrogen-positive breast and gynecological cancers. Those studies discovered that cancers fueled by the estrogen hormone also benefit from byproducts of cholesterol. These substances act like estrogen and further spark cancer growth.
The team also found that estrogen-negative breast cancer does not depend on estrogen to metastasize. Despite these results, high cholesterol still made this form of the disease worse.
With those findings in mind, McDonnell’s team looked at cancer in mice and uncovered that migrating cancer cells consume cholesterol in response to stress. Although most of the cancer cells die, study authors say this process lives by the motto “what doesn’t kill you makes you stronger.”
Those cancer cells that gobble up cholesterol and live end up with a “superpower” that allows them to withstand ferroptosis, a natural biological process which kills cells through stress. As a result, these stress-impervious cancer cells can move freely and spread the disease to the rest of the body.
Moreover, researchers say other types of cancer use cholesterol in this manner, including melanoma.
“Unraveling this pathway has highlighted new approaches that may be useful for the treatment of advanced disease,” McDonnell concludes. “There are contemporary therapies under development that inhibit the pathway we’ve described. Importantly, these findings yet again highlight why lowering cholesterol — either using drugs or by dietary modification — is a good idea for better health.”
The study appears in the journal Nature Communications.