Figure 1. FGFR signaling pathway in breast cancer.

The binding of FGFs to the extracellular domain of FGFR induces dimerization of the receptor and phosphorylation of its intracellular C-terminal domain. The C-terminal phosphorylated tyrosine residues serve as anchors for adaptor proteins that, in turn, activate four distinct signaling cascades: RAS-RAF-MEK-MAPK, PI3K-AKT, JAK-STAT and PLCγ. The activation of these pathways ultimately promotes the expression of transcriptional profiles associated with cell proliferation, differentiation, migration, drug resistance and ERα signaling. TME: tumor microenvironment; HSPG: heparan sulfate proteoglycan; FGFs fibroblast growth factors; FGFR: fibroblast growth factor receptor; PLCγ: phospholipase Cγ; PIP2: phosphatidylinositol-4,5-biphosphate; DAG: diacylglicerol; IP3: inositol triphosphate; PKC: protein kinase C; FRS2α: FGFR substrate 2α; GRB2: growth factor receptor-bound 2; GAB1: GRB2-associated binding protein 1; SOS: son of sevenless; PI3K: phosphatidylinositol-4,5-bisphosphate 3-kinase; JAK: janus activated kinase; STAT: signal transducer and activator of transcription; ERα: estrogen receptor α.