Forkhead box C1

FOXC1
Identifiers
Aliases	FOXC1, ARA, FKHL7, FREAC-3, FREAC3, IGDA, IHG1, IRID1, RIEG3, forkhead box C1, ASGD3
External IDs	OMIM: 601090 MGI: 1347466 HomoloGene: 20373 GeneCards: FOXC1
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6p25.3 Start 1,609,915 bp[1] End 1,613,897 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13 A3.2|13 13.52 cM Start 31,990,616 bp[2] End 31,996,459 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in parotid gland vena cava trigeminal ganglion renal medulla palpebral conjunctiva tibia endothelial cell nipple urethra glomerulus Top expressed in parotid gland lacrimal gland stria vascularis interatrial septum calvaria ascending aorta conjunctival fornix pulmonary valve utricle optic nerve More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding sequence-specific DNA binding RNA polymerase II transcription regulatory region sequence-specific DNA binding DNA-binding transcription activator activity, RNA polymerase II-specific protein binding transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding DNA binding, bending transcription coactivator binding transcription coactivator activity transcription factor binding promoter-specific chromatin binding DNA-binding transcription factor activity DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component nucleoplasm nucleus cytosol Biological process eye development somitogenesis Notch signaling pathway skeletal system development glycosaminoglycan metabolic process positive regulation of hematopoietic progenitor cell differentiation regulation of transcription, DNA-templated neural crest cell development paraxial mesoderm formation ossification vascular endothelial growth factor signaling pathway collagen fibril organization maintenance of lens transparency heart morphogenesis in utero embryonic development cardiac muscle cell proliferation lymph vessel development transcription, DNA-templated embryonic heart tube development positive regulation of hematopoietic stem cell differentiation odontogenesis of dentin-containing tooth positive regulation of transcription, DNA-templated ventricular cardiac muscle tissue morphogenesis heart development blood vessel remodeling brain development vascular endothelial growth factor receptor signaling pathway negative regulation of lymphangiogenesis blood vessel development positive regulation of gene expression mesenchymal cell differentiation mesenchymal cell development artery morphogenesis ovarian follicle development negative regulation of angiogenesis camera-type eye development regulation of organ growth germ cell migration lacrimal gland development negative regulation of mitotic cell cycle negative regulation of apoptotic process involved in outflow tract morphogenesis transcription by RNA polymerase II endochondral ossification cell population proliferation positive regulation of epithelial to mesenchymal transition cell migration positive regulation of DNA binding positive regulation of transcription by RNA polymerase II cellular response to epidermal growth factor stimulus positive regulation of core promoter binding negative regulation of transcription by RNA polymerase II cerebellum development positive regulation of keratinocyte differentiation glomerular epithelium development ureteric bud development kidney development chemokine-mediated signaling pathway cellular response to chemokine angiogenesis multicellular organism development regulation of transcription by RNA polymerase II anatomical structure morphogenesis cell differentiation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2296 17300 Ensembl ENSG00000054598 ENSMUSG00000050295 UniProt Q12948 Q61572 RefSeq (mRNA) NM_001453 NM_008592 RefSeq (protein) NP_001444 NP_032618 Location (UCSC) Chr 6: 1.61 – 1.61 Mb Chr 13: 31.99 – 32 Mb PubMed search [3] [4]
Wikidata
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Forkhead box C1, also known as FOXC1, is a protein which in humans is encoded by the FOXC1 gene.^[5][6][7]

Function

This gene belongs to the forkhead family of transcription factors which is characterized by a distinct DNA-binding fork head domain. The specific function of this gene has not yet been determined; however, it has been shown to play a role in the regulation of embryonic and ocular development.

Heart development and somitogenesis

FOXC1 and its close relative, FOXC2 are both critical components in the development of the heart and blood vessels, as well as the segmentation of the paraxial mesoderm and the formation of somites. Expression of the Fox proteins range from low levels in the posterior pre-somitic mesoderm (PSM) to the highest levels in the anterior PSM. Homozygous mutant embryos for both Fox proteins failed to form somites 1–8, which indicates the importance of these proteins early on in somite development.^[8]

In cardiac morphogenesis, FOXC1 and FOXC2 are required for the proper development of the cardiac outflow tract. The outflow tract forms from a cell population known as the secondary heart field. The Fox proteins are transcribed in the secondary heart field where they regulate the expression of key signaling molecules such as Fgf8, Fgf10, Tbx1, Isl1, and Bmp4.^[9]

Clinical significance

Mutations in this gene cause various glaucoma phenotypes including primary congenital glaucoma, autosomal dominant iridogoniodysgenesis anomaly, and Axenfeld–Rieger syndrome type 3.^[5] FOXC1 mutations are also found in association with Dandy–Walker malformation.^[10]

Role in cancer

FOXC1 induces the epithelial to mesenchymal transition (EMT), which is a process where epithelial cells separate from surrounding cells and begin migration. This process is involved in metastasis, giving FOXC1 a crucial role in cancer. The over expression of FOXC1 results in the up-regulation of fibronectin, vimentin, and N-cadherin, which contribute to cellular migration in nasopharyngeal carcinoma (NPC). The knockout of FOXC1 in human NPC cells down-regulated vimentin, fibronectin, and N-cadherin expression.^[11]

FOXC1 transcription factor regulates EMT in basal-like breast cancer (BLBC). Activation of SMO-independent Hedgehog signaling by FOXC1 alters the cancer stem cell (CSC) properties in BLBC cells.^[12] These CSCs, which are regulated by FOXC1 signaling, contribute to tumor proliferation, tissue invasion, and relapse.^[13]

See also

• FOX proteins

References

Further reading

External links

• FOXC1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This page was last edited on 3 December 2023, at 10:03