FGFR4


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FGFR4

A gene on chromosome 5q35.1-qter that encodes fibroblast growth factor receptor-4, which has an extracellular region composed of 3 immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The function of FGFR4 is unknown.

Molecular pathology
FGFR4 is overexpressed in gynaecological tumours, suggesting a role in breast and ovarian malignancies.
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Approximately 30% of patients with HCC have tumors with aberrantly activated FGFR4 signaling.
Fgfr3 and Fgfr4 null mutant mice, on the other hand, are viable with no reproductive phenotype reported (20-22).
FGFR1 and FGFR3 are expressed in well-differentiated thyroid cancers, and ATC cells overexpress FGFR4 [35].
tropicalis, FGFR3 is expressed in the developing lens, FGFR2 is prominently expressed in corneal epithelium, and FGFR1 and FGFR4 are expressed in "cells surrounding the lens" in early tadpoles (Lea et al., 2009).
"We found interesting results for genetic variations in two genes, FGFR4 and Klotho-beta, both of which are crucial in allowing the hormone FGF19, secreted by the enterocytes in the ileum, to signal the liver and its hepatocytes to shut off further bile acid production," said Dr.
According to the researchers, these findings are the first to show that when FGFR4 is overactive, it plays a key role in the growth and spread of RMS and that the gene could be an important target for therapy in the future.
Two of the four genes encoding the FGFRs, fgfr1 and fgfr4, showed statistically significant treatment-related changes in expression, but the magnitude of the effect on fgfr1 was quite small, < 10% (Figure 3).
Discovered and developed in-house by Eisai, LENVIMA is an orally administered kinase inhibitor with a novel binding mode that selectively inhibits the multi activities of vascular endothelial growth factor (VEGF) receptors (VEGFR1, VEGFR2 and VEGFR3) and fibroblast growth factor (FGF) receptors (FGFR1, FGFR2, FGFR3 and FGFR4) in addition to other pathway-related RTKs (including the platelet-derived growth factor (PDGF) receptor PDGFRalpha; KIT; and RET) involved in tumor angiogenesis, tumor progression and modification of tumor immunity.
Finally, analyses of cotreatment also evidenced the gene-specific nature of the response to n-3 PUFAs; that is, genes such as MRP2 (Figure 1(d)) were additively activated by EPA and DHA, while, for FGFR4 (Figure 1(d)), CYP7A1, or CYP27 (SF3), the presence of the 2 n-3 PUFAs did not lead to improved regulatory events, when compared to each omega-3 alone.
Another study using chromatin immunoprecipitation-on-chip analyses demonstrated that FGFR4 is a direct downstream target of Pax3 in mouse embryo [30].
FGFR1, FGFR2, FGFR3, and FGFR4 are fibroblast growth factor receptors belonging to the RTK family [14].
About 71% of the tumors in this subtype have a p53 mutation and activation of receptor tyrosine kinase pathways, such as FGFR4, EGFR, and HER2; and 39% of tumors have a PIK3CA mutation.