FOXA1

FOXA1
Identifiers
Aliases	FOXA1, HNF3A, TCF3A, forkhead box A1
External IDs	OMIM: 602294 MGI: 1347472 HomoloGene: 3307 GeneCards: FOXA1
Gene location (Human)
Chr.	Chromosome 14 (human)[1]
End	37,596,059 bp[1]
Gene location (Mouse)
Chr.	Chromosome 12 (mouse)[2]
End	57,546,916 bp[2]
Gene ontology
Molecular function	• sequence-specific DNA binding; • protein domain specific binding; • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific; • transcription factor binding; • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity; • DNA binding; • GO:0001948 protein binding; • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific;
Cellular component	• microvilli; • cell nucleus; • fibrillar center; • nucleoplasm;
Biological process	• Notch signaling pathway; • prostate gland stromal morphogenesis; • dopaminergic neuron differentiation; • positive regulation of intracellular estrogen receptor signaling pathway; • response to estradiol; • regulation of transcription, DNA-templated; • lung morphogenesis; • glucose homeostasis; • positive regulation of smoothened signaling pathway; • lung development; • regulation of transcription from RNA polymerase II promoter; • neuron fate specification; • anatomical structure formation involved in morphogenesis; • positive regulation of mitotic cell cycle; • positive regulation of sequence-specific DNA binding transcription factor activity; • negative regulation of transcription from RNA polymerase II promoter; • transcription from RNA polymerase II promoter; • tube morphogenesis; • secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development; • transcription, DNA-templated; • regulation of cell cycle; • multicellular organism development; • prostate gland epithelium morphogenesis; • connective tissue development; • positive regulation of neuron differentiation; • epithelial cell maturation involved in prostate gland development; • regulation of gene expression; • lung epithelial cell differentiation; • dorsal/ventral neural tube patterning; • epithelial-mesenchymal signaling involved in prostate gland development; • epithelial tube branching involved in lung morphogenesis; • respiratory basal cell differentiation; • hormone metabolic process; • alveolar secondary septum development; • negative regulation of epithelial to mesenchymal transition; • positive regulation of cell-cell adhesion mediated by cadherin; • positive regulation of transcription from RNA polymerase II promoter; • chromatin remodeling; • anatomical structure morphogenesis; • positive regulation of apoptotic process; • chromatin organization; • cell differentiation;
	Sources:Amigo / QuickGO
Orthologs
	3169
	15375
	ENSG00000129514
	ENSMUSG00000035451
	P55317
	P35582
	NM_004496
	NM_008259
	NP_004487
	NP_032285
	Wikidata
View/Edit Human	View/Edit Mouse

Forkhead box protein A1 (FOXA1), also known as hepatocyte nuclear factor 3-alpha (HNF-3A), is a protein that in humans is encoded by the FOXA1 gene.[5][6][7]

Function

FOXA1 is a member of the forkhead class of DNA-binding proteins. These hepatocyte nuclear factors are transcriptional activators for liver-specific transcripts such as albumin and transthyretin, and they also interact with chromatin as a pioneer factor. Similar family members in mice have roles in the regulation of metabolism and in the differentiation of the pancreas and liver.[5]

Marker in breast cancer

FOXA1 in breast cancer is highly correlated with ERα⁺, GATA3⁺, and PR⁺ protein expression as well as endocrine signaling. FOXA1 acts as a pioneer factor for ERa in ERα⁺ breast cancer, and its expression might identify ERα⁺ cancers that undergo rapid reprogramming of ERa signaling that is associated with poor outcomes and treatment resistance.[8] Conversely, in ERα⁻ breast cancer FOXA1 is highly correlated with low-grade morphology and improved disease free survival. FOXA1 is a downstream target of GATA3 in the mammary gland.[9] Expression in ERα⁻ cancers may identify a subset of tumors that is responsive to other endocrine therapies such as androgen receptor antagonist treatment.[10][11]

Role in cancer

Mutations in this gene have been recurrently seen in instances of prostate cancer.[12]

Expression of FOXA1 correlates with two EMT markers, namely Twist1 and E-cadherin in breast cancer.[13]

References

GRCh38: Ensembl release 89: ENSG00000129514 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000035451 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Entrez Gene: forkhead box A1".
Bingle CD, Gowan S (1996). "Molecular cloning of the forkhead transcription factor HNF-3 alpha from a human pulmonary adenocarcinoma cell line". Biochim Biophys Acta. 1307 (1): 17–20. doi:10.1016/0167-4781(96)00058-9. PMID 8652662.
Mincheva A, Lichter P, Schütz G, Kaestner KH (1997). "Assignment of the human genes for hepatocyte nuclear factor 3-alpha, -beta, and -gamma (HNF3A, HNF3B, HNF3G) to 14q12-q13, 20p11, and 19q13.2-q13.4". Genomics. 39 (3): 417–9. doi:10.1006/geno.1996.4477. PMID 9119385.
Ross-Innes CS, Stark R, Teschendorff AE, Holmes KA, Ali HR, Dunning MJ, Brown GD, Gojis O, Ellis IO, Green AR, Ali S, Chin SF, Palmieri C, Caldas C, Carroll JS (4 January 2012). "Differential oestrogen receptor binding is associated with clinical outcome in breast cancer". Nature. 481 (7381): 389–93. doi:10.1038/nature10730. PMC 3272464. PMID 22217937.
Kouros-Mehr H, Slorach EM, Sternlicht MD, Werb Z (December 2006). "GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland". Cell. 127 (5): 1041–55. doi:10.1016/j.cell.2006.09.048. PMC 2646406. PMID 17129787.
Albergaria A, Paredes J, Sousa B, Milanezi F, Carneiro V, Bastos J, Costa S, Vieira D, Lopes N, Lam EW, Lunet N, Schmitt F (2009). "Expression of FOXA1 and GATA-3 in breast cancer: The prognostic significance in hormone receptor-negative tumours". Breast Cancer Research. 11 (3): R40. doi:10.1186/bcr2327. PMC 2716509. PMID 19549328.
Sanga S, Broom BM, Cristini V, Edgerton ME (2009). "Gene expression meta-analysis supports existence of molecular apocrine breast cancer with a role for androgen receptor and implies interactions with ErbB family". BMC Medical Genomics. 2: 59. doi:10.1186/1755-8794-2-59. PMC 2753593. PMID 19747394.
Barbieri CE, Baca SC, Lawrence MS, Demichelis F, Blattner M, Theurillat JP, White TA, Stojanov P, Van Allen E, Stransky N, Nickerson E, Chae SS, Boysen G, Auclair D, Onofrio RC, Park K, Kitabayashi N, MacDonald TY, Sheikh K, Vuong T, Guiducci C, Cibulskis K, Sivachenko A, Carter SL, Saksena G, Voet D, Hussain WM, Ramos AH, Winckler W, Redman MC, Ardlie K, Tewari AK, Mosquera JM, Rupp N, Wild PJ, Moch H, Morrissey C, Nelson PS, Kantoff PW, Gabriel SB, Golub TR, Meyerson M, Lander ES, Getz G, Rubin MA, Garraway LA (June 2012). "Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer". Nat. Genet. 44 (6): 685–9. doi:10.1038/ng.2279. PMC 3673022. PMID 22610119.
BenAyed-Guerfali, Dorra; Dabbèche-Bouricha, Emna; Ayadi, Wajdi; Trifa, Fatma; Charfi, Slim; Khabir, Abdelmajid; Sellami-Boudawara, Tahia; Mokdad-Gargouri, Raja (2019). "Association of FOXA1 and EMT markers (Twist1 and E-cadherin) in breast cancer". Molecular Biology Reports. 46 (3): 3247–3255. doi:10.1007/s11033-019-04784-w. ISSN 0301-4851. PMID 30941644.

External links

FactorBook FOXA1

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

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000129514 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000035451 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] "Entrez Gene: forkhead box A1".

[pmid8652662-6] Bingle CD, Gowan S (1996). "Molecular cloning of the forkhead transcription factor HNF-3 alpha from a human pulmonary adenocarcinoma cell line". Biochim Biophys Acta. 1307 (1): 17–20. doi:10.1016/0167-4781(96)00058-9. PMID 8652662.

[pmid9119385-7] Mincheva A, Lichter P, Schütz G, Kaestner KH (1997). "Assignment of the human genes for hepatocyte nuclear factor 3-alpha, -beta, and -gamma (HNF3A, HNF3B, HNF3G) to 14q12-q13, 20p11, and 19q13.2-q13.4". Genomics. 39 (3): 417–9. doi:10.1006/geno.1996.4477. PMID 9119385.

[8] Ross-Innes CS, Stark R, Teschendorff AE, Holmes KA, Ali HR, Dunning MJ, Brown GD, Gojis O, Ellis IO, Green AR, Ali S, Chin SF, Palmieri C, Caldas C, Carroll JS (4 January 2012). "Differential oestrogen receptor binding is associated with clinical outcome in breast cancer". Nature. 481 (7381): 389–93. doi:10.1038/nature10730. PMC 3272464. PMID 22217937.

[pmid17129787-9] Kouros-Mehr H, Slorach EM, Sternlicht MD, Werb Z (December 2006). "GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland". Cell. 127 (5): 1041–55. doi:10.1016/j.cell.2006.09.048. PMC 2646406. PMID 17129787.

[Albergaria_2009-10] Albergaria A, Paredes J, Sousa B, Milanezi F, Carneiro V, Bastos J, Costa S, Vieira D, Lopes N, Lam EW, Lunet N, Schmitt F (2009). "Expression of FOXA1 and GATA-3 in breast cancer: The prognostic significance in hormone receptor-negative tumours". Breast Cancer Research. 11 (3): R40. doi:10.1186/bcr2327. PMC 2716509. PMID 19549328.

[Sanga_2009-11] Sanga S, Broom BM, Cristini V, Edgerton ME (2009). "Gene expression meta-analysis supports existence of molecular apocrine breast cancer with a role for androgen receptor and implies interactions with ErbB family". BMC Medical Genomics. 2: 59. doi:10.1186/1755-8794-2-59. PMC 2753593. PMID 19747394.

[Barbieri_2012-12] Barbieri CE, Baca SC, Lawrence MS, Demichelis F, Blattner M, Theurillat JP, White TA, Stojanov P, Van Allen E, Stransky N, Nickerson E, Chae SS, Boysen G, Auclair D, Onofrio RC, Park K, Kitabayashi N, MacDonald TY, Sheikh K, Vuong T, Guiducci C, Cibulskis K, Sivachenko A, Carter SL, Saksena G, Voet D, Hussain WM, Ramos AH, Winckler W, Redman MC, Ardlie K, Tewari AK, Mosquera JM, Rupp N, Wild PJ, Moch H, Morrissey C, Nelson PS, Kantoff PW, Gabriel SB, Golub TR, Meyerson M, Lander ES, Getz G, Rubin MA, Garraway LA (June 2012). "Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer". Nat. Genet. 44 (6): 685–9. doi:10.1038/ng.2279. PMC 3673022. PMID 22610119.

[13] BenAyed-Guerfali, Dorra; Dabbèche-Bouricha, Emna; Ayadi, Wajdi; Trifa, Fatma; Charfi, Slim; Khabir, Abdelmajid; Sellami-Boudawara, Tahia; Mokdad-Gargouri, Raja (2019). "Association of FOXA1 and EMT markers (Twist1 and E-cadherin) in breast cancer". Molecular Biology Reports. 46 (3): 3247–3255. doi:10.1007/s11033-019-04784-w. ISSN 0301-4851. PMID 30941644.