Both WWP1 and ITCH facilitate this process: WWP1 inhibits BC bone metastasis by enhancing CXCL12-mediated CXCR4 lysosomal translocation and degradation (Subik et al., 2012), while ITCH ubiquitinates CXCR4 at the plasma membrane for lysosomal degradation (Marchese et al., 2003). This evidence concerns the gene CXCR4 and breast cancer.