The Role of Cdo1 in Ferroptosis and Apoptosis in Cancer.

Abstract

Cysteine dioxygenase type 1 (Cdo1) is a tumor suppressor gene. It regulates the metabolism of cysteine, thereby influencing the cellular antioxidative capacity. This function puts Cdo1 in a prominent position to promote ferroptosis and apoptosis. Cdo1 promotes ferroptosis mainly by decreasing the amounts of antioxidants, leading to autoperoxidation of the cell membrane through Fenton reaction. Cdo1 promotes apoptosis mainly through the product of cysteine metabolism, taurine, and low level of antioxidants. Many cancers exhibit altered function of Cdo1, underscoring its crucial role in cancer cell survival. Genetic and epigenetic alterations have been found, with methylation of Cdo1 promoter as the most common mutation. The fact that no cancer was found to be caused by altered Cdo1 function alone indicates that the tumor suppressor role of Cdo1 is mild. By compiling the current knowledge about apoptosis, ferroptosis, and the role of Cdo1, this review suggests possibilities for how the mild anticancer role of Cdo1 could be harnessed in new cancer therapies. Here, developing drugs targeting Cdo1 is considered meaningful in neoadjuvant therapies, for example, helping against the development of anti-cancer drug resistance in tumor cells.