NOTCH3 and breast cancer: In the tumor microenvironment of BC, a secreted protein named Cartilage Oligomeric Matrix Protein (COMP) physically bridges Notch3 and JAG1 on the cell membrane of CSCs, thus driving JAG1/Notch3 signaling and subsequently activating the β-catenin and Akt signaling pathways to maintain CSC status (Papadakos et al., 2019).