Fig. 8

Brief figure summarizes the FGF2-FGFR1-p21 regulatory pathway in FGFR1 amplified ER + BC cells. FGF ligands can activate both the classical FGFR MAPK cascade to promote proliferation and a collateral JAK-STAT signaling to upregulate p21, which leads to a growth inhibitory effect and a stem cell-like state. In cancer cells with FGFR1 amplification, FGF ligands addition leads to enhanced upregulation of p21 and stem cell-like state. By using a range of inhibitors target different nodes of FGFR signaling, including FGFR1 (PD186866), pan-FGFR (TAS-120), JAK2 (AZD1480), STAT1 (Fludarabine), STAT3 (BAY2353), CBP/P300 (SGC-CBP30), ERK1/2 (Ulixertinib), and p21 (UC2288), these different states could be reversed