Chronically high cholesterol levels are known to be associated with an increased risk of breast cancer and worsening outcomes for most cancers, according to studies.
Researchers at the Duke Cancer Institute have released an online report describing how breast cancer cells use cholesterol to develop tolerance to stress, making them impervious to death as they migrate from the original tumor site.
Donald McDonnell Prof. of Cancer Biology Duke Cancer Institute
“Most cancer cells die as they try to metastasize or migrate, it’s a very stressful process. 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. Importantly, the findings yet again highlight why lowering cholesterol either using drugs or by dietary modification is a good idea for better health.”
Mr. McDonnell built on earlier research in the lab focusing on the link between high cholesterol and estrogen-positive breast and gynecological cancers. Cancers driven by the estrogen hormone benefited from cholesterol derivatives that act like estrogen, boosting cancer growth, according to those research.
However, a dilemma arose in the case of estrogen-negative breast tumors. Although these malignancies are not estrogen-dependent, high cholesterol is still associated with worse disease, suggesting a different mechanism might be at work. In the current study using cancer cell lines and mouse models, the Duke researchers found that migrating cancer cells gobble cholesterol in response to stress and most of them died.
But in the what-doesn’t-kill-you-makes-you-stronger motif, those that live to emerge with a super-power that makes them able to withstand ferroptosis, a natural process in which cells succumb to stress. These stress-impervious cancer cells then proliferate and readily metastasize.
The process appears to be used not only by estrogen-negative breast cancer cells but other types of tumors, including melanoma. And the mechanisms identified could be targeted by therapies.
“Unraveling this pathway has highlighted new approaches that may be useful for the treatment of advanced disease. There are contemporary therapies under development that inhibit the pathway we’ve described,” Mr. McDonnell said.
