The fibroblast growth factor (FGF) 7 subfamily, consisting of FGF3, FGF7 (the founding member), FGF10, and FGF22, is unique among FGF subfamily members in that its members are secreted exclusively from the mesenchyme and specifically activate epithelial cells lined by the FGFR1b and FGFR2b isoforms. This unidirectional mesenchymal-to-epithelial signaling contributes to the developmental regulation of essentially all organs, glands, and limbs.
(Data source: Francavilla C, et al. Open Biol. 2022)
Members of the FGF7 subfamily are essential for organogenesis and tissue patterning in the embryo and for mediating wound healing and tissue homeostasis in adult mammals: FGF3 is required for inner ear development; FGF7 is required for kidney, thymus, and hippocampus development; FGF10 is required for limb, lung, thyroid, pituitary, lacrimal, and salivary gland development; and FGF22 is responsible for presynaptic neural differentiation.
(Data source: AlphaFold)
FGF7 is composed of 194 amino acids and is a secreted extracellular protein. The main functional domain is the 32-194 segment, which includes an N-type glycosylation modification.
(Data source: Uniprot)
FGF7 is widely expressed in tissues and produced by various cells (i.e., fibroblasts, endothelial cells, smooth muscle cells, and dendritic epidermal T cells).
(Data source: Protein Atlas)
FGF7 induces the MAPK pathway and PI3K/AKT pathway to promote the expression of E11 and connexin Cx43, thereby promoting dendrite elongation and intercellular communication.
(Data source: Liu X, et al. Int J Biol Sci. 2021)
The FGF7 & FGFR2 signaling axis results in a wide range of tumor-promoting and drug-resistant properties in tumor diseases. For example, FGF7-FGFR2 autocrine signaling increases the growth of fusion-positive rhabdomyosarcoma and NVP-BGJ398 chemotherapy resistance.
(Data source: Milton CI, et al. Mol Oncol. 2022.)
The Wnt-TCF7-SOX9 axis promotes cholangiocarcinoma proliferation and pemigatinib resistance via the FGF7-FGFR2 autocrine pathway;
(Data source: Liu Z, et al. Oncogene. 2022)
FGF7 & FGFR2-JunB signaling counteracts the inhibitory effect of progesterone P4 on luminal breast cancer cells;
(Data source: Mieczkowski K, et al. Mol Oncol. 2022)
Cancer-associated fibroblasts (CAFs) exhibit extensive heterogeneity and functional differences. Recently, researchers have for the first time divided lung cancer CAFs into three subtypes and provided personalized clinical treatment strategies for each subtype. The classification is primarily based on the regulation of the signaling axis by FGF7 and FGFR2 abundance, which in turn influences drug resistance.
(Data source: Hu H, et al. Cancer Cell. 2021)
Currently, the main research direction of FGF7 is to promote cancer resistance, and the key point is also around the downstream regulation of the FGF7&FGFR2b signaling axis. The targeted development of FGFR2b inhibitors is a major idea to solve the problem of related drug tolerance.
