Schematic representation of signals involved in paracrine mediation of systemic oestrogen signalling. The signal sending cell (white) responds to oestrogen (E2) and initiates EGFR, FGFR and Notch ligand production. A signalling cascade is initiated within the signal receiving cell (grey) which includes, but may not be limited to ERK, Tbx3 and Pea3 signalling. This drives increased CSC activity. This signal mediation can be blocked by tamoxifen, gefitinib and gamma secretase inhibitors (GSI).