Forkhead box C1

FOXC1
Identifiers
Aliases	FOXC1, ARA, FKHL7, FREAC-3, FREAC3, IGDA, IHG1, IRID1, RIEG3, forkhead box C1, ASGD3
External IDs	MGI: 1347466 HomoloGene: 20373 GeneCards: FOXC1
Gene location (Human)
Chr.	Chromosome 6 (human)[1]
End	1,613,897 bp[1]
Gene location (Mouse)
Chr.	Chromosome 13 (mouse)[2]
End	31,812,476 bp[2]
RNA expression pattern
	More reference expression data
Gene ontology
Molecular function	• DNA binding; • sequence-specific DNA binding; • RNA polymerase II regulatory region sequence-specific DNA binding; • transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding; • 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; • transcription factor activity, sequence-specific DNA binding; • transcription regulatory region DNA binding; • RNA polymerase II transcription factor activity, sequence-specific DNA binding;
Cellular component	• nucleoplasm; • nuclear heterochromatin; • cell 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 blood vessel size; • 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 from RNA polymerase II promoter; • endochondral ossification; • cell proliferation; • positive regulation of epithelial to mesenchymal transition; • cell migration; • positive regulation of DNA binding; • positive regulation of transcription from RNA polymerase II promoter; • cellular response to epidermal growth factor stimulus; • positive regulation of core promoter binding; • negative regulation of transcription from RNA polymerase II promoter; • 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 from RNA polymerase II promoter; • anatomical structure morphogenesis; • cell differentiation;
	Sources:Amigo / QuickGO
Orthologs
	2296
	17300
	ENSG00000054598
	ENSMUSG00000050295
	Q12948
	Q61572
	NM_001453
	NM_008592
	NP_001444
	NP_032618
	Wikidata
View/Edit Human	View/Edit Mouse

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. Mutations in this gene cause various glaucoma phenotypes including primary congenital glaucoma, autosomal dominant iridogoniodysgenesis anomaly, and Axenfeld-Rieger anomaly.^[5]

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]

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.^[10]

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.^[11] These CSCs, which are regulated by FOXC1 signaling, contribute to tumor proliferation, tissue invasion, and relapse.^[12]

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000054598 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000050295 - Ensembl, May 2017
↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
1 2 "Entrez Gene: FOXC1 forkhead box C1".
↑ 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 395442. PMID 7957066.
↑ 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.
↑ 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 312788. PMID 11562355.
↑ 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.
↑ 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 4758279. PMID 26461269.
↑ 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 4806384. PMID 26565916.
↑ 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 4806384. PMID 26565916.

External links

FOXC1+protein,+human at the US 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 article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000054598 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000050295 - Ensembl, May 2017

[3] "Human PubMed Reference:".

[4] "Mouse PubMed Reference:".

[entrez-5] 1 2 "Entrez Gene: FOXC1 forkhead box C1".

[pmid7957066-6] 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 395442. PMID 7957066.

[pmid9620769-7] 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.

[pmid11562355-8] 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 312788. PMID 11562355.

[9] 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.

[pmid26461269-10] 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 4758279. PMID 26461269.

[11] 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 4806384. PMID 26565916.

[pmid26565916-12] 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 4806384. PMID 26565916.