Given the intracellular interactions and consistent subcellular distributions between USP11 and p21, we speculate that USP11's role as a tumor suppressor is associated with its nuclear localization and nuclear p21, such as in lung cancer, whereas the cytoplasmic localization of USP11 contributes to oncogenic effects through cytoplasmic p21, such as in breast cancer. This evidence concerns the gene CDKN1A and breast carcinoma.