Figure 1.

FGFRs-mediated mechanisms of cancer development and progression. Fibroblast growth factor receptors (FGFRs) and their natural ligands (FGFs) are involved in many biological processes, crucial for the proper operating of the cells and entire organism. However, many aberrations in FGFRs and/or FGFs genes may generate deregulations in the FGFRs/FGFs axis, which often upregulate downstream cell signaling and drive tumorigenesis. Activating mutations may lead to ligand-independent receptor dimerization and activation or creating the constitutively active kinase domains. The amplification of FGFRs or FGFs genes results in protein overexpression, which may also contribute to enhanced FGFRs-mediated cell signaling. Chromosomal translocations lead to the formation of fusion proteins that in some cases cause, similarly to activation mutations, receptor activation independently of FGFs presence. Regardless of the type of FGFRs dysfunction, the consequence is upregulated cell signaling that may drive cancer progression, through uncontrolled cell division, apoptosis avoidance, new blood vessel formation and/or EMT.