Fgfr1, or fibroblast growth factor receptor 1, is a transmembrane cytokine receptor crucial for early human embryo development, involved in gastrulation, organ specification, and tissue patterning. It is associated with multiple biological pathways, and its activity is mediated through phospholipase-C-gamma (PLCγ) and activation of nuclear factor-κB (NF-κB) in macrophages [1]. It also plays a role in regulating intracellular protein degradation pathways of IRP2 in prostate cancer cells, thus governing iron homeostasis [3].

In atherosclerosis, deletion of myeloid-expressed Fgfr1 in Apoe-/-mice reduces atherosclerotic lesions and lipid accumulations, indicating that macrophage-derived Fgfr1 drives atherosclerosis via the PLCγ-mediated activation of the NF-κB inflammatory signalling pathway [1]. In prostate cancer, deletion of Fgfr1 in DU145 cells decreases the labile iron pool (LIP), suggesting its role in cancer progression [3].

In conclusion, Fgfr1 is essential for embryo development and tissue patterning. Model-based research, especially gene knockout in mice, has revealed its role in diseases like atherosclerosis and prostate cancer. Understanding Fgfr1 function provides potential therapeutic targets for these and other associated diseases, such as Kallmann syndrome, congenital scoliosis, and tooth agenesis as identified in various studies [2,4,5].

References:

1. Wang, Lintao, Luo, Wu, Zhang, Suya, Xu, Biao, Liang, Guang. . Macrophage-derived FGFR1 drives atherosclerosis through PLCγ-mediated activation of NF-κB inflammatory signalling pathway. In Cardiovascular research, 120, 1385-1399. doi:10.1093/cvr/cvae131. https://pubmed.ncbi.nlm.nih.gov/38842387/

2. Villanueva, C, de Roux, N. 2010. FGFR1 mutations in Kallmann syndrome. In Frontiers of hormone research, 39, 51-61. doi:10.1159/000312693. https://pubmed.ncbi.nlm.nih.gov/20389085/

3. Lin, Hui, Lin, Shuaijun, Shi, Liuhong, Pan, Xuebo, Wang, Cong. 2024. FGFR1 governs iron homeostasis via regulating intracellular protein degradation pathways of IRP2 in prostate cancer cells. In Communications biology, 7, 1011. doi:10.1038/s42003-024-06704-6. https://pubmed.ncbi.nlm.nih.gov/39154074/

4. Wang, Shengru, Chai, Xiran, Yan, Zihui, Zhang, Terry Jianguo, Wu, Nan. 2021. Novel FGFR1 Variants Are Associated with Congenital Scoliosis. In Genes, 12, . doi:10.3390/genes12081126. https://pubmed.ncbi.nlm.nih.gov/34440300/

5. Yao, Siyue, Zhou, Xi, Gu, Min, Ma, Lan, Pan, Yongchu. 2023. FGFR1 variants contributed to families with tooth agenesis. In Human genomics, 17, 93. doi:10.1186/s40246-023-00539-8. https://pubmed.ncbi.nlm.nih.gov/37833774/