Some types of cancer have a relentless appetite for the metabolite cholesterol, using as much as they can access to accelerate their growth beyond the capabilities of normal cells. Research by scientists at Sanford Burnham Prebys Medical Discovery Institute and collaborators at the University of Illinois Chicago have now unveiled a potential method for turning the table on these tumors by subverting their cholesterol cravings. The researchers’ studies, in mice and in human cancer cells, revealed new insights into enzymes known as phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) that help move cholesterol around cells. The researchers showed that without the help of these enzymes, a cholesterol traffic jam occurs, blocking the cancer cell’s ability to fuel tumor growth. Headed by Brooke Emerling, PhD, the director of and associate professor in the Cancer Metabolism and Microenvironment Program at the Sanford Burnham Prebys NCI-Designated Cancer Center, the team reported on its findings in Science Advances, in a paper titled “Noncanonical PI(4,5)P2 coordinates lysosome positioning through cholesterol trafficking.” The TP53 gene is mutated in roughly half of all cancers. Emerling and first author Ryan Loughran, PhD, a postdoctoral associate in the Emerling lab, focus on difficult-to-treat forms of breast cancer, where TP53 mutations are found in more than 84% of triple-negative breast cancers and three of every four HER2-amplified breast cancers. Cancer cells with a mutation in the tumor-suppressing TP53 gene are known to produce extra cholesterol. This may make them more vulnerable to starvation if scientists can put a stop to the steady supply of the lipid. “We need more ways to treat…
