This conclusion is documented by the following discoveries: First, USP22 is further upregulated in BCSCs and breast cancer and targeted USP22 deletion dramatically impaired BCSC self-renewal and tumorigenicity; Second, USP22 controls breast cancer cell stemness through integrin b1 upregulation; Third, USP22 functions as a bona fide deubiquitinase of the ITGB1 transcription FoxM1 and promotes BCSC self-renewal through FoxM1-mediated integrin b1 expression. The gene discussed is ITGB1; the disease is breast cancer.