The fibroblast growth factor (FGF) family is one of the largest growth factor families, consisting of 18 intrinsic tissue regulatory polypeptides that share similarities in structure and amino acid sequence. The FGFs are broadly expressed, regulating cell proliferation, differentiation, survival, and function. The FGFs elicit their regulatory activities by binding and activating the FGF receptor (FGFR) transmembrane tyrosine kinases encoded by four highly homologous genes. Alongside the FGF and FGFR, the FGF signaling complex also includes highly diverse heparan sulfate (HS) polysaccharides and klothos as co-receptors that not only affect the ligand-binding activity, but also modulate signaling specificity of the FGFR. Binding of the FGF to the FGFR-HS complex changes its conformation, leading to receptor autophosphorylation, as well as phosphorylation of downstream signaling molecules, thus, conveying the signals to downstream effectors.
As an intrinsic cell signaling axis, the FGF and FGFR are expressed almost ubiquitously in all tissues and stages, functioning either in autocrine, paracrine, or endocrine mechanisms. These intrinsic FGF signaling axes play important roles in embryonic development, adult tissue regeneration, homeostasis and function. Redundant FGF and FGFR expression is common in multiple tissues and organs to warrant signaling conveyance, with a loss of FGF signaling having been reported as the culprit for developmental disorders and diseases.
On the other hand, ectopic FGF signaling is pathological and has been found to underlie various diseases, ranging from birth defects and metabolic disorders, to cancer and cardiovascular disease. Multiple mechanisms have been attributed to aberrant FGF signaling, including ectopic expression of FGF, FGFR, and heparan sulfate proteoglycans (HSPG), gain-of-function mutations in the FGFR tyrosine kinases, and possibly other unidentified mechanisms. Several pathways have been shown to convey FGF signaling, including FGFR substrate 2a (FRS2a), the mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), phospholipase C? (PLC?), STAT3, P38, and JNK. However, how FGF elicits cell type-specific pathological signals is poorly understood, although it is suspected that simply the long duration and high intensity of the signals play a causative role.
The aim of this Research Topic is to highlight significant scientific breakthroughs related, but not limited, to intrinsic FGF signaling in regulatory development, as well as ectopic FGF signaling in birth defects, cell metabolic disorders, and cancer. Manuscripts of interest will focus either on the FGF, FGFR, heparan sulfate proteoglycan, klothos, as well as their signaling cascades. We welcome the submission of the following article types: Original Research, Review, General Commentary, Opinion, and Protocols.
The fibroblast growth factor (FGF) family is one of the largest growth factor families, consisting of 18 intrinsic tissue regulatory polypeptides that share similarities in structure and amino acid sequence. The FGFs are broadly expressed, regulating cell proliferation, differentiation, survival, and function. The FGFs elicit their regulatory activities by binding and activating the FGF receptor (FGFR) transmembrane tyrosine kinases encoded by four highly homologous genes. Alongside the FGF and FGFR, the FGF signaling complex also includes highly diverse heparan sulfate (HS) polysaccharides and klothos as co-receptors that not only affect the ligand-binding activity, but also modulate signaling specificity of the FGFR. Binding of the FGF to the FGFR-HS complex changes its conformation, leading to receptor autophosphorylation, as well as phosphorylation of downstream signaling molecules, thus, conveying the signals to downstream effectors.
As an intrinsic cell signaling axis, the FGF and FGFR are expressed almost ubiquitously in all tissues and stages, functioning either in autocrine, paracrine, or endocrine mechanisms. These intrinsic FGF signaling axes play important roles in embryonic development, adult tissue regeneration, homeostasis and function. Redundant FGF and FGFR expression is common in multiple tissues and organs to warrant signaling conveyance, with a loss of FGF signaling having been reported as the culprit for developmental disorders and diseases.
On the other hand, ectopic FGF signaling is pathological and has been found to underlie various diseases, ranging from birth defects and metabolic disorders, to cancer and cardiovascular disease. Multiple mechanisms have been attributed to aberrant FGF signaling, including ectopic expression of FGF, FGFR, and heparan sulfate proteoglycans (HSPG), gain-of-function mutations in the FGFR tyrosine kinases, and possibly other unidentified mechanisms. Several pathways have been shown to convey FGF signaling, including FGFR substrate 2a (FRS2a), the mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), phospholipase C? (PLC?), STAT3, P38, and JNK. However, how FGF elicits cell type-specific pathological signals is poorly understood, although it is suspected that simply the long duration and high intensity of the signals play a causative role.
The aim of this Research Topic is to highlight significant scientific breakthroughs related, but not limited, to intrinsic FGF signaling in regulatory development, as well as ectopic FGF signaling in birth defects, cell metabolic disorders, and cancer. Manuscripts of interest will focus either on the FGF, FGFR, heparan sulfate proteoglycan, klothos, as well as their signaling cascades. We welcome the submission of the following article types: Original Research, Review, General Commentary, Opinion, and Protocols.
