Forkhead box C1

FOXC1
Identifiers
Aliases FOXC1, ARA, FKHL7, FREAC-3, FREAC3, IGDA, IHG1, IRID1, RIEG3, forkhead box C1
External IDs MGI: 1347466 HomoloGene: 20373 GeneCards: FOXC1
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez

2296

17300

Ensembl

ENSG00000054598

ENSMUSG00000050295

UniProt

Q12948

Q61572

RefSeq (mRNA)

NM_001453

NM_008592

RefSeq (protein)

NP_001444.2

NP_032618.2

Location (UCSC) Chr 6: 1.61 – 1.61 Mb Chr 13: 31.81 – 31.81 Mb
PubMed search [1] [2]
Wikidata
View/Edit HumanView/Edit Mouse

Forkhead box C1, also known as FOXC1, is a protein which in humans is encoded by the FOXC1 gene.[3][4][5]

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. Mutations in this gene cause various glaucoma phenotypes including primary congenital glaucoma, autosomal dominant iridogoniodysgenesis anomaly, and Axenfeld-Rieger anomaly.[3]

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.[6]

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.[7]

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.[8]

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.[9] These CSCs, which are regulated by FOXC1 signaling, contribute to tumor proliferation, tissue invasion, and relapse.[10]

See also

References

  1. ↑ "Human PubMed Reference:".
  2. ↑ "Mouse PubMed Reference:".
  3. 1 2 "Entrez Gene: FOXC1 forkhead box C1".
  4. ↑ Pierrou S, Hellqvist M, Samuelsson L, Enerbäck S, Carlsson P (October 1994). "Cloning and characterization of seven human forkhead proteins: binding site specificity and DNA bending". The EMBO Journal. 13 (20): 5002–12. PMC 395442Freely accessible. PMID 7957066.
  5. ↑ Nishimura DY, Swiderski RE, Alward WL, Searby CC, Patil SR, Bennet SR, Kanis AB, Gastier JM, Stone EM, Sheffield VC (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. PMID 9620769.
  6. ↑ Kume T, Jiang H, Topczewska JM, Hogan BL (September 2001). "The murine winged helix transcription factors, Foxc1 and Foxc2, are both required for cardiovascular development and somitogenesis". Genes & Development. 15 (18): 2470–82. doi:10.1101/gad.907301. PMC 312788Freely accessible. PMID 11562355.
  7. ↑ Seo S, Kume T. Forkhead transcription factors, Foxc1 and Foxc2, are required for the morphogenesis of the cardiac outflow tract. Developmental biology. 2006:421-436.
  8. ↑ Ou-Yang L, Xiao SJ, Liu P, Yi SJ, Zhang XL, Ou-Yang S, Tan SK, Lei X (December 2015). "Forkhead box C1 induces epithelial‑mesenchymal transition and is a potential therapeutic target in nasopharyngeal carcinoma". Molecular Medicine Reports. 12 (6): 8003–9. doi:10.3892/mmr.2015.4427. PMC 4758279Freely accessible. PMID 26461269.
  9. ↑ Han, Bingchen; Qu, Ying; Jin, Yanli; Yu, Yi; Deng, Nan; Wawrowsky, Kolja; Zhang, Xiao; Li, Na; Bose, Shikha. "FOXC1 Activates Smoothened-Independent Hedgehog Signaling in Basal-like Breast Cancer". Cell Reports. 13 (5): 1046–1058. doi:10.1016/j.celrep.2015.09.063. PMC 4806384Freely accessible. PMID 26565916.
  10. ↑ Han B, Qu Y, Jin Y, Yu Y, Deng N, Wawrowsky K, Zhang X, Li N, Bose S, Wang Q, Sakkiah S, Abrol R, Jensen TW, Berman BP, Tanaka H, Johnson J, Gao B, Hao J, Liu Z, Buttyan R, Ray PS, Hung MC, Giuliano AE, Cui X (November 2015). "FOXC1 Activates Smoothened-Independent Hedgehog Signaling in Basal-like Breast Cancer". Cell Reports. 13 (5): 1046–58. doi:10.1016/j.celrep.2015.09.063. PMC 4806384Freely accessible. PMID 26565916.

Further reading

External links

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

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