ESR1 and breast cancer: Besides, a recent study has also shown that sphingosine-1-phosphate (S1P) promotes CSC expansion via S1P receptor 3 and subsequent Notch1 activation in estrogen receptor (ER)-positive breast cancer cells45, suggesting that activation of Notch1 signaling in breast CSCs might be mediated through both Notch ligand-dependent and -independent pathways.