NOTCH signaling is activated by cell-to-cell interaction: NOTCH receptor (NOTCH 1, 2, 3 and 4) contact with ligands (Delta or Jagged proteins), prompting the release of NOTCH intracellular domain (NICD, Cleaved NOTCH1, activated NOTCH1), which then subsequently diffuses into the nucleus and interact with the co-activators to activate downstream events [16–20], and also contributed to the sphere formation ability of breast cancer stem cells [21, 22]. Here, NOTCH1 is linked to breast cancer.