This gene belongs to theforkhead family oftranscription factors which is characterized by a distinct DNA-bindingfork 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.
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 asFgf8,Fgf10,Tbx1,Isl1, andBmp4.[9]
Mutations in this gene cause variousglaucoma phenotypes including primary congenital glaucoma, autosomal dominant iridogoniodysgenesis anomaly, andAxenfeld–Rieger syndrome type 3.[5] FOXC1 mutations are also found in association withDandy–Walker malformation.[10]
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 offibronectin,vimentin, andN-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]
^Nishimura DY, Swiderski RE, Alward WL, Searby CC, Patil SR, Bennet SR, et al. (June 1998). "The forkhead transcription factor gene FKHL7 is responsible for glaucoma phenotypes which map to 6p25".Nature Genetics.19 (2):140–7.doi:10.1038/493.PMID9620769.S2CID34692231.
^Seo S, Kume T (2006). "Forkhead transcription factors, Foxc1 and Foxc2, are required for the morphogenesis of the cardiac outflow tract".Developmental Biology.296 (2):421–436.doi:10.1016/j.ydbio.2006.06.012.PMID16839542.
Sperling R, Bustin M (July 1975). "Dynamic equilibrium in histone assembly: self-assembly of single histones and histone pairs".Biochemistry.14 (15):3322–31.doi:10.1021/bi00686a006.PMID1170889.
Larsson C, Hellqvist M, Pierrou S, White I, Enerbäck S, Carlsson P (December 1995). "Chromosomal localization of six human forkhead genes, freac-1 (FKHL5), -3 (FKHL7), -4 (FKHL8), -5 (FKHL9), -6 (FKHL10), and -8 (FKHL12)".Genomics.30 (3):464–9.doi:10.1006/geno.1995.1266.PMID8825632.
Nishimura DY, Swiderski RE, Alward WL, Searby CC, Patil SR, Bennet SR, et al. (June 1998). "The forkhead transcription factor gene FKHL7 is responsible for glaucoma phenotypes which map to 6p25".Nature Genetics.19 (2):140–7.doi:10.1038/493.PMID9620769.S2CID34692231.
Wang WH, McNatt LG, Shepard AR, Jacobson N, Nishimura DY, Stone EM, et al. (April 2001). "Optimal procedure for extracting RNA from human ocular tissues and expression profiling of the congenital glaucoma gene FOXC1 using quantitative RT-PCR".Molecular Vision.7:89–94.PMID11320352.
Kawase C, Kawase K, Taniguchi T, Sugiyama K, Yamamoto T, Kitazawa Y, et al. (December 2001). "Screening for mutations of Axenfeld-Rieger syndrome caused by FOXC1 gene in Japanese patients".Journal of Glaucoma.10 (6):477–82.doi:10.1097/00061198-200112000-00007.PMID11740218.S2CID43165728.
Freyaldenhoven BS, Fried C, Wielckens K (July 2002). "FOXD4a and FOXD4b, two new winged helix transcription factors, are expressed in human leukemia cell lines".Gene.294 (1–2):131–140.doi:10.1016/S0378-1119(02)00702-3.PMID12234674.
