XU Chenqi lab contributes a review discussing cholesterol metabolism in cancer

Cholesterol metabolism plays important roles in health and disease. Modulating cholesterol metabolism has become an emerging avenue to treat multiple types of cancer. HUANG Binlu and XU Chenqi at SIBCB worked together SONG Bao-Liang at Wuhan University to write a review article discussing this fast-developing field that is now published at Nature Metabolism.

 

Cholesterol is an essential building block of cell membranes and a precursor to bile acids and steroid hormones.  Beyond these roles, cholesterol metabolites have a variety of biological functions that are poorly understood thus far. As fast-proliferating cells, cancer cells reprogram cholesterol metabolism to support membrane biogenesis and other functional needs. Higher levels of cholesterol biosynthesis, uptake, esterification and oxidation have been observed with various types of cancer cells, driven by intrinsic and extrinsic factors. Tumor microenvironment is often enriched with oxidized cholesterol species, named oxysterols, which have potent immune modulation functions.

 

Typically, oxysterols suppress immune effector cells and promote immune suppressor cells, thus causing an immune suppressive environment to promote tumor progression. Interfering cholesterol metabolism of cancer cells and immune cells shows promising results in clinical and preclinical studies. In addition to numerous works with cholesterol biosynthesis inhibitors such as statin, drugs targeting the cholesterol esterification enzyme and the key transcriptional factor Liver X receptor have been developed and tested in different cancer models. Combinations with existing anti-cancer therapies have also been proven effectively. New therapeutic opportunities in cancer therefore emerge and might eventually benefit patients in the near future.