With regard to E3 ubiquitin ligase ITCH of Notch3, research has shown that[63] ITCH can regulate the degradation of the tumor suppressor gene p63 and its improper removal is also closely related to malignant transformation and chemical resistance.[64] However, it has also been reported that[59] the activation of ITCH can mediate the ubiquitination and endocytosis of the chemokine receptor CXCR4, thereby reducing the stemness of breast cancer cells. This evidence concerns the gene ITCH and breast cancer.