The Role of CDCA3 in Disulfidptosis: Implications for Breast Cancer Cell Viability and Treatment

"Disulfidptosis" is a novel concept, primarily characterized by the depletion of intracellular NADPH during glucose deprivation, leading to the accumulation of disulfides. This accumulation triggers disulfide stress, breakdown of the actin cytoskeleton, and ultimately, cell death. Breast cancer, being a highly prevalent cancer type, requires a substantial amount of glucose for its rapid growth and division. Glucose deprivation induces rapid cell death, possibly associated with the process of disulfidptosis. In this study, we developed a novel signature based on 10 machine learning algorithms integration. Compared to the traditional TNM staging, this new predictive model demonstrates superior predictive capabilities. Among the 13 genes included in the signature, CDCA3, a cell cycle-regulating protein, is expressed at higher levels in breast cancer. Our experiments indicate that breast cancer cells (SKBR-3 and MCF-7 lines) with downregulated expression of CDCA3 through shRNA exhibit reduced proliferation, migration, and invasion capabilities compared to the WT cells. Conversely, breast cancer cells with forced overexpression of CDCA3 show enhanced growth and mobility. Moreover, observations of primary and immortalized breast cancer cells in a glucose-deprived environment reveal that overexpressing CDCA3 can slow down the process of cell cytoskeleton contraction under starvation conditions, while knockdown CDCA3 accelerates this change. In conclusion, CDCA3, associated with the process of disulfidptosis, may represent a new target for breast cancer treatment.