CCAR2 and breast carcinoma: We also found that in human breast cancer tissue DBC1 expression was reduced in hypoxic regions (Figure 6G), and the downregulation of DBC1 was found to be negatively correlated with clinical stage and the percentage of the Ki67-positive cell population (Figure 6H and I and Supplementary file 2), further indicating that under pathological conditions SIAH2-mediated DBC1 ubiquitination and degradation are beneficial for tumor progression.