SNAI1
Zinc finger protein SNAI1 is a protein that in humans is encoded by the SNAI1 gene.[1][2] Snail is a family of transcription factors that promote the repression of the adhesion molecule E-cadherin to regulate epithelial to mesenchymal transition (EMT) during embryonic development.
Function
The Drosophila embryonic protein SNAI1, commonly known as Snail, is a zinc finger transcriptional repressor which downregulates the expression of ectodermal genes within the mesoderm. The nuclear protein encoded by this gene is structurally similar to the Drosophila snail protein, and is also thought to be critical for mesoderm formation in the developing embryo. At least two variants of a similar processed pseudogene have been found on chromosome 2.[2] SNAI1 zinc-fingers (ZF) binds to E-box, an E-cadherin promoter region[3], and represses the expression of the adhesion molecule, which induces the tightly bound epithelial cells to break loose from each other and migrate into the developing embryo to become mesenchymal cells. This process allows for the formation of the mesodermal layer in the developing embryo. Though SNAI1 is shown to repress expression of E-cadherin in epithelial cells, studies have shown homozygous mutant embryos are still able to form a mesodermal layer[4]. However, the mesodermal layer present shows characteristics of epithelial cells and not mesenchymal cells (the mutant mesoderm cells exhibited a polarized state). Other studies show that mutation of specific ZFs contribute to a decrease in SNAI1 E-cadherin repression[5].
Clinical significance
SNAIL gene may show a role in recurrence of breast cancer by downregulating E-cadherin and inducing an epithelial to mesenchymal transition.[6] The process of EMT is also noted as an important and noteworthy process in tumor growth, through the invasion and metastasis of tumor cells due to repression of E-cadherin adhesion molecules. Through knockout models, one study has shown the importance of SNAI1 in the growth of breast cancer cells[7]. Knockout models showed significant reduction in cancer invasiveness and therefore can be used as a therapeutic measure for the treatment of breast cancer before chemotherapy treatment[8].
Interactions
SNAI1 has been shown to interact with CTDSPL,[9] CTDSP1[9] and CTDSP2.[9]
References
- ↑ Paznekas WA, Okajima K, Schertzer M, Wood S, Jabs EW (February 2000). "Genomic organization, expression, and chromosome location of the human SNAIL gene (SNAI1) and a related processed pseudogene (SNAI1P)". Genomics 62 (1): 42–9. doi:10.1006/geno.1999.6010. PMID 10585766.
- ↑ 2.0 2.1 "Entrez Gene: SNAI1 snail homolog 1 (Drosophila)".
- ↑ Villarejo, Ana; Cortes-Cabrera, Alvaro; Molina-Ortiz, Patricia; Portillo, Francisco; Cano, Amparo (2013). "Differential Role of Snail1 and Snail2 Zinc Fingers in E-cadherin Repression and Epithelial to Mesenchymal Transition". The Journal of Biological Chemistry 289 (2): 930–41. doi:10.1074/jbc.M113.528026.
- ↑ Carver, Ethan A.; Jiang, Rulang; Lan, Yu; Oram, Kathleen F.; Gridley, Thomas (December 2001). "The Mouse Snail Gene Encodes a Key Regulator of the Epithelial-Mesenchymal Transition". Molecular and Cellular Biology 21 (23): 8184–88. doi:10.1128/MCB.21.23.8181-8188.2001.
- ↑ Villarejo, Ana; Cortes-Cabrera, Alvaro; Molina-Ortiz, Patricia; Portillo, Francisco; Cano, Amparo (2013). "Differential Role of Snail1 and Snail2 Zinc Fingers in E-cadherin Repression and Epithelial to Mesenchymal Transition". The Journal of Biological Chemistry 298 (2): 930–41. doi:10.1074/jbc.M113.528026.
- ↑ Davidson NE, Sukumar S (September 2005). "Of Snail, mice, and women". Cancer Cell 8 (3): 173–4. doi:10.1016/j.ccr.2005.08.006. PMID 16169460.
- ↑ Olmeda, David; Moreno-Bueno, Gema; Flores, Juana M.; Fabra, Angels; Portillo, Francisco; Cano, Amparo (December 15, 2007). "SNAI1 Is Required for Tumor Growth and Lymph Node Metastasis of Human Breast Carcinoma MDA-MB-231 Cells". American Association for Cancer Research 67 (24): 11721–31. doi:10.1158/0008-5472.
- ↑ Olmeda, David; Moreno-Bueno, Gema; Flores, Juana M.; Fabra, Angels; Portillo, Francisco; Cano, Amparo (December 15, 2007). "SNAI1 Is Required for Tumor Growth and Lymph Node Metastasis of Human Breast Carcinoma MDA-MB-231 Cells". American Association for Cancer Research 67 (24): 11721–31. doi:10.1158/0008-5472.
- ↑ 9.0 9.1 9.2 Wu Y, Evers BM, Zhou BP (January 2009). "Small C-terminal domain phosphatase enhances snail activity through dephosphorylation". J. Biol. Chem. 284 (1): 640–8. doi:10.1074/jbc.M806916200. PMC 2610500. PMID 19004823.
Further reading
- Twigg SR, Wilkie AO (1999). "Characterisation of the human snail (SNAI1) gene and exclusion as a major disease gene in craniosynostosis.". Hum. Genet. 105 (4): 320–6. doi:10.1007/s004390051108. PMID 10543399.
- Batlle E, Sancho E, Francí C et al. (2000). "The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells.". Nat. Cell Biol. 2 (2): 84–9. doi:10.1038/35000034. PMID 10655587.
- Smith S, Metcalfe JA, Elgar G (2000). "Identification and analysis of two snail genes in the pufferfish (Fugu rubripes) and mapping of human SNA to 20q.". Gene 247 (1–2): 119–28. doi:10.1016/S0378-1119(00)00110-4. PMID 10773451.
- Okubo T, Truong TK, Yu B et al. (2001). "Down-regulation of promoter 1.3 activity of the human aromatase gene in breast tissue by zinc-finger protein, snail (SnaH)". Cancer Res. 61 (4): 1338–46. PMID 11245431.
- Deloukas P, Matthews LH, Ashurst J et al. (2002). "The DNA sequence and comparative analysis of human chromosome 20". Nature 414 (6866): 865–71. doi:10.1038/414865a. PMID 11780052.
- Blanco MJ, Moreno-Bueno G, Sarrio D et al. (2002). "Correlation of Snail expression with histological grade and lymph node status in breast carcinomas". Oncogene 21 (20): 3241–6. doi:10.1038/sj.onc.1205416. PMID 12082640.
- Guaita S, Puig I, Franci C et al. (2002). "Snail induction of epithelial to mesenchymal transition in tumor cells is accompanied by MUC1 repression and ZEB1 expression". J. Biol. Chem. 277 (42): 39209–16. doi:10.1074/jbc.M206400200. PMID 12161443.
- Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Yokoyama K, Kamata N, Fujimoto R et al. (2003). "Increased invasion and matrix metalloproteinase-2 expression by Snail-induced mesenchymal transition in squamous cell carcinomas". Int. J. Oncol. 22 (4): 891–8. doi:10.3892/ijo.22.4.891. PMID 12632084.
- Ikenouchi J, Matsuda M, Furuse M, Tsukita S (2004). "Regulation of tight junctions during the epithelium-mesenchyme transition: direct repression of the gene expression of claudins/occludin by Snail". J. Cell. Sci. 116 (Pt 10): 1959–67. doi:10.1242/jcs.00389. PMID 12668723.
- Domínguez D, Montserrat-Sentís B, Virgós-Soler A et al. (2003). "Phosphorylation regulates the subcellular location and activity of the snail transcriptional repressor". Mol. Cell. Biol. 23 (14): 5078–89. doi:10.1128/MCB.23.14.5078-5089.2003. PMC 162233. PMID 12832491.
- Imai T, Horiuchi A, Wang C et al. (2003). "Hypoxia attenuates the expression of E-cadherin via up-regulation of SNAIL in ovarian carcinoma cells". Am. J. Pathol. 163 (4): 1437–47. doi:10.1016/S0002-9440(10)63501-8. PMC 1868286. PMID 14507651.
- Miyoshi A, Kitajima Y, Sumi K et al. (2004). "Snail and SIP1 increase cancer invasion by upregulating MMP family in hepatocellular carcinoma cells". Br. J. Cancer 90 (6): 1265–73. doi:10.1038/sj.bjc.6601685. PMC 2409652. PMID 15026811.
- Ohkubo T, Ozawa M (2004). "The transcription factor Snail downregulates the tight junction components independently of E-cadherin downregulation". J. Cell. Sci. 117 (Pt 9): 1675–85. doi:10.1242/jcs.01004. PMID 15075229.
- Barberà MJ, Puig I, Domínguez D et al. (2004). "Regulation of Snail transcription during epithelial to mesenchymal transition of tumor cells". Oncogene 23 (44): 7345–54. doi:10.1038/sj.onc.1207990. PMID 15286702.
- Beausoleil SA, Jedrychowski M, Schwartz D et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
- Kajita M, McClinic KN, Wade PA (2004). "Aberrant expression of the transcription factors snail and slug alters the response to genotoxic stress". Mol. Cell. Biol. 24 (17): 7559–66. doi:10.1128/MCB.24.17.7559-7566.2004. PMC 506998. PMID 15314165.
- Zhou BP, Deng J, Xia W et al. (2004). "Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial-mesenchymal transition". Nat. Cell Biol. 6 (10): 931–40. doi:10.1038/ncb1173. PMID 15448698.
- Saito T, Oda Y, Kawaguchi K et al. (2004). "E-cadherin mutation and Snail overexpression as alternative mechanisms of E-cadherin inactivation in synovial sarcoma". Oncogene 23 (53): 8629–38. doi:10.1038/sj.onc.1207960. PMID 15467754.