FOXA1
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 (June 1996). "Molecular cloning of the forkhead transcription factor HNF-3 alpha from a human pulmonary adenocarcinoma cell line". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1307 (1): 17–20. doi:10.1016/0167-4781(96)00058-9. PMID 8652662.
- Mincheva A, Lichter P, Schütz G, Kaestner KH (February 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): 417–419. doi:10.1006/geno.1996.4477. PMID 9119385.
- Ross-Innes CS, Stark R, Teschendorff AE, Holmes KA, Ali HR, Dunning MJ, et al. (January 2012). "Differential oestrogen receptor binding is associated with clinical outcome in breast cancer". Nature. 481 (7381): 389–393. Bibcode:2012Natur.481..389R. 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): 1041–1055. doi:10.1016/j.cell.2006.09.048. PMC 2646406. PMID 17129787.
- Albergaria A, Paredes J, Sousa B, Milanezi F, Carneiro V, Bastos J, et al. (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 (September 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, et al. (May 2012). "Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer". Nature Genetics. 44 (6): 685–689. doi:10.1038/ng.2279. PMC 3673022. PMID 22610119.
- BenAyed-Guerfali D, Dabbèche-Bouricha E, Ayadi W, Trifa F, Charfi S, Khabir A, et al. (June 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. PMID 30941644. S2CID 91190545.
Further reading
- Song L, Xu Z, Zhang C, Qiao X, Huang C (August 2009). "Up-regulation of the HSP72 by Foxa1 in MCF-7 human breast cancer cell line". Biochemical and Biophysical Research Communications. 386 (1): 30–34. doi:10.1016/j.bbrc.2009.05.120. PMID 19486887.
- Zhang Y, Ali TZ, Zhou H, D'Souza DR, Lu Y, Jaffe J, et al. (January 2010). "ErbB3 binding protein 1 represses metastasis-promoting gene anterior gradient protein 2 in prostate cancer". Cancer Research. 70 (1): 240–248. doi:10.1158/0008-5472.CAN-09-2904. PMC 3724404. PMID 20048076.
- McMullin RP, Dobi A, Mutton LN, Orosz A, Maheshwari S, Shashikant CS, Bieberich CJ (January 2010). "A FOXA1-binding enhancer regulates Hoxb13 expression in the prostate gland". Proceedings of the National Academy of Sciences of the United States of America. 107 (1): 98–103. Bibcode:2010PNAS..107...98M. doi:10.1073/pnas.0902001107. PMC 2806740. PMID 20018680.
- Sun Q, Yu X, Degraff DJ, Matusik RJ (December 2009). "Upstream stimulatory factor 2, a novel FoxA1-interacting protein, is involved in prostate-specific gene expression". Molecular Endocrinology. 23 (12): 2038–2047. doi:10.1210/me.2009-0092. PMC 2796152. PMID 19846536.
- Liu N, Niu Y, Wang SL, Yu Q, Zhang RJ, Liu TJ (May 2010). "[Diagnostic and prognostic significance of FOXA1 expression in molecular subtypes of breast invasive ductal carcinomas]". Zhonghua Yi Xue Za Zhi. 90 (20): 1403–1407. PMID 20646630.
- Haiman CA, Garcia RR, Hsu C, Xia L, Ha H, Sheng X, et al. (January 2009). "Screening and association testing of common coding variation in steroid hormone receptor co-activator and co-repressor genes in relation to breast cancer risk: the Multiethnic Cohort". BMC Cancer. 9: 43. doi:10.1186/1471-2407-9-43. PMC 2637888. PMID 19183483.
- Kohler S, Cirillo LA (January 2010). "Stable chromatin binding prevents FoxA acetylation, preserving FoxA chromatin remodeling". The Journal of Biological Chemistry. 285 (1): 464–472. doi:10.1074/jbc.M109.063149. PMC 2804194. PMID 19897491.
- Malik S, Jiang S, Garee JP, Verdin E, Lee AV, O'Malley BW, et al. (January 2010). "Histone deacetylase 7 and FoxA1 in estrogen-mediated repression of RPRM". Molecular and Cellular Biology. 30 (2): 399–412. doi:10.1128/MCB.00907-09. PMC 2798473. PMID 19917725.
- Motallebipour M, Ameur A, Reddy Bysani MS, Patra K, Wallerman O, Mangion J, et al. (2009). "Differential binding and co-binding pattern of FOXA1 and FOXA3 and their relation to H3K4me3 in HepG2 cells revealed by ChIP-seq". Genome Biology. 10 (11): R129. doi:10.1186/gb-2009-10-11-r129. PMC 3091322. PMID 19919681.
- Eeckhoute J, Lupien M, Meyer CA, Verzi MP, Shivdasani RA, Liu XS, Brown M (March 2009). "Cell-type selective chromatin remodeling defines the active subset of FOXA1-bound enhancers". Genome Research. 19 (3): 372–380. doi:10.1101/gr.084582.108. PMC 2661808. PMID 19129543.
- Nakshatri H, Badve S (April 2007). "FOXA1 as a therapeutic target for breast cancer". Expert Opinion on Therapeutic Targets. 11 (4): 507–514. doi:10.1517/14728222.11.4.507. PMID 17373880. S2CID 923953.
- Iacobazzi V, Infantino V, Bisaccia F, Castegna A, Palmieri F (July 2009). "Role of FOXA in mitochondrial citrate carrier gene expression and insulin secretion". Biochemical and Biophysical Research Communications. 385 (2): 220–224. doi:10.1016/j.bbrc.2009.05.030. hdl:11586/126284. PMID 19445897.
- Nucera C, Eeckhoute J, Finn S, Carroll JS, Ligon AH, Priolo C, et al. (June 2009). "FOXA1 is a potential oncogene in anaplastic thyroid carcinoma". Clinical Cancer Research. 15 (11): 3680–3689. doi:10.1158/1078-0432.CCR-08-3155. PMID 19470727.
- Nakshatri H, Badve S (March 2009). "FOXA1 in breast cancer". Expert Reviews in Molecular Medicine. 11: e8. doi:10.1017/S1462399409001008. PMID 19261198. S2CID 10940765.
- Song Y, Washington MK, Crawford HC (March 2010). "Loss of FOXA1/2 is essential for the epithelial-to-mesenchymal transition in pancreatic cancer". Cancer Research. 70 (5): 2115–2125. doi:10.1158/0008-5472.CAN-09-2979. PMC 2831111. PMID 20160041.
- Lee HJ, Chattopadhyay S, Yoon WH, Bahk JY, Kim TH, Kang HS, Lee K (March 2010). "Overexpression of hepatocyte nuclear factor-3alpha induces apoptosis through the upregulation and accumulation of cytoplasmic p53 in prostate cancer cells". The Prostate. 70 (4): 353–361. doi:10.1002/pros.21069. PMID 19866472. S2CID 20375911.
- Bernardo GM, Lozada KL, Miedler JD, Harburg G, Hewitt SC, Mosley JD, et al. (June 2010). "FOXA1 is an essential determinant of ERalpha expression and mammary ductal morphogenesis". Development. 137 (12): 2045–2054. doi:10.1242/dev.043299. PMC 2875844. PMID 20501593.
- Albergaria A, Paredes J, Sousa B, Milanezi F, Carneiro V, Bastos J, et al. (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.
- Huang QY, Li GH, Kung AW (August 2009). "The -9247 T/C polymorphism in the SOST upstream regulatory region that potentially affects C/EBPalpha and FOXA1 binding is associated with osteoporosis". Bone. 45 (2): 289–294. doi:10.1016/j.bone.2009.03.676. PMID 19371798.
- Sano M, Aoyagi K, Takahashi H, Kawamura T, Mabuchi T, Igaki H, et al. (February 2010). "Forkhead box A1 transcriptional pathway in KRT7-expressing esophageal squamous cell carcinomas with extensive lymph node metastasis". International Journal of Oncology. 36 (2): 321–330. doi:10.3892/ijo_00000503. PMID 20043065.
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