SNAI1

Snail family zinc finger 1
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2Y48​, 3W5K​
Identifiers
Symbols	SNAI1 ; SLUGH2; SNA; SNAH; SNAIL; SNAIL1; dJ710H13.1
External IDs	OMIM: 604238 MGI: 98330 HomoloGene: 4363 GeneCards: SNAI1 Gene
Gene ontology Molecular function • RNA polymerase II regulatory region sequence-specific DNA binding • transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding • protein binding • kinase binding • metal ion binding Cellular component • nucleus • cytoplasm Biological process • negative regulation of transcription from RNA polymerase II promoter • osteoblast differentiation • mesoderm formation • epithelial to mesenchymal transition • positive regulation of epithelial to mesenchymal transition • negative regulation of vitamin D biosynthetic process • cell migration • positive regulation of cell migration • hair follicle morphogenesis • negative regulation of DNA damage response, signal transduction by p53 class mediator • positive regulation of transcription, DNA-templated • palate development • cartilage morphogenesis • trophoblast giant cell differentiation • negative regulation of cell differentiation involved in embryonic placenta development • left/right pattern formation • Notch signaling involved in heart development • negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage • regulation of bicellular tight junction assembly Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6615	20613
Ensembl	ENSG00000124216	ENSMUSG00000042821
UniProt	O95863	Q02085
RefSeq (mRNA)	NM_005985	NM_011427
RefSeq (protein)	NP_005976	NP_035557
Location (UCSC)	Chr 20: 49.98 – 49.99 Mb	Chr 2: 167.54 – 167.54 Mb
PubMed search

Zinc finger protein SNAI1 (sometime referred to as Snail) 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.^[3]

Clinical significance

Snail gene may show a role in recurrence of breast cancer by downregulating E-cadherin and inducing an epithelial to mesenchymal transition.^[5] 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.^[6] 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.^[6]

Interactions

SNAI1 has been shown to interact with CTDSPL,^[7] CTDSP1^[7] and CTDSP2.^[7]

References

1. Paznekas WA, Okajima K, Schertzer M, Wood S, Jabs EW (Nov 1999). "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. "Entrez Gene: SNAI1 snail homolog 1 (Drosophila)".
3. Villarejo A, Cortés-Cabrera A, Molina-Ortíz P, Portillo F, Cano A (Jan 2014). "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. PMC 3887216. PMID 24297167.
4. 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.
5. Davidson NE, Sukumar S (Sep 2005). "Of Snail, mice, and women". Cancer Cell 8 (3): 173–4. doi:10.1016/j.ccr.2005.08.006. PMID 16169460.
6. 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.can-07-2318.
7. Wu Y, Evers BM, Zhou BP (Jan 2009). "Small C-terminal domain phosphatase enhances snail activity through dephosphorylation". The Journal of Biological Chemistry 284 (1): 640–8. doi:10.1074/jbc.M806916200. PMC 2610500. PMID 19004823.

Further reading

• Twigg SR, Wilkie AO (Oct 1999). "Characterisation of the human snail (SNAI1) gene and exclusion as a major disease gene in craniosynostosis". Human Genetics 105 (4): 320–6. doi:10.1007/s004390051108. PMID 10543399.
• Batlle E, Sancho E, Francí C, Domínguez D, Monfar M, Baulida J, García De Herreros A (Feb 2000). "The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells". Nature Cell Biology 2 (2): 84–9. doi:10.1038/35000034. PMID 10655587.
• Smith S, Metcalfe JA, Elgar G (Apr 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, Itoh T, Zhao J, Grube B, Zhou D, Chen S (Feb 2001). "Down-regulation of promoter 1.3 activity of the human aromatase gene in breast tissue by zinc-finger protein, snail (SnaH)". Cancer Research 61 (4): 1338–46. PMID 11245431.
• Blanco MJ, Moreno-Bueno G, Sarrio D, Locascio A, Cano A, Palacios J, Nieto MA (May 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, Garrido M, Dominguez D, Batlle E, Sancho E, Dedhar S, De Herreros AG, Baulida J (Oct 2002). "Snail induction of epithelial to mesenchymal transition in tumor cells is accompanied by MUC1 repression and ZEB1 expression". The Journal of Biological Chemistry 277 (42): 39209–16. doi:10.1074/jbc.M206400200. PMID 12161443.
• Yokoyama K, Kamata N, Fujimoto R, Tsutsumi S, Tomonari M, Taki M, Hosokawa H, Nagayama M (Apr 2003). "Increased invasion and matrix metalloproteinase-2 expression by Snail-induced mesenchymal transition in squamous cell carcinomas". International Journal of Oncology 22 (4): 891–8. doi:10.3892/ijo.22.4.891. PMID 12632084.
• Ikenouchi J, Matsuda M, Furuse M, Tsukita S (May 2003). "Regulation of tight junctions during the epithelium-mesenchyme transition: direct repression of the gene expression of claudins/occludin by Snail". Journal of Cell Science 116 (Pt 10): 1959–67. doi:10.1242/jcs.00389. PMID 12668723.
• Domínguez D, Montserrat-Sentís B, Virgós-Soler A, Guaita S, Grueso J, Porta M, Puig I, Baulida J, Francí C, García de Herreros A (Jul 2003). "Phosphorylation regulates the subcellular location and activity of the snail transcriptional repressor". Molecular and Cellular Biology 23 (14): 5078–89. doi:10.1128/MCB.23.14.5078-5089.2003. PMC 162233. PMID 12832491.
• Imai T, Horiuchi A, Wang C, Oka K, Ohira S, Nikaido T, Konishi I (Oct 2003). "Hypoxia attenuates the expression of E-cadherin via up-regulation of SNAIL in ovarian carcinoma cells". The American Journal of Pathology 163 (4): 1437–47. doi:10.1016/S0002-9440(10)63501-8. PMC 1868286. PMID 14507651.
• Miyoshi A, Kitajima Y, Sumi K, Sato K, Hagiwara A, Koga Y, Miyazaki K (Mar 2004). "Snail and SIP1 increase cancer invasion by upregulating MMP family in hepatocellular carcinoma cells". British Journal of Cancer 90 (6): 1265–73. doi:10.1038/sj.bjc.6601685. PMC 2409652. PMID 15026811.
• Ohkubo T, Ozawa M (Apr 2004). "The transcription factor Snail downregulates the tight junction components independently of E-cadherin downregulation". Journal of Cell Science 117 (Pt 9): 1675–85. doi:10.1242/jcs.01004. PMID 15075229.
• Barberà MJ, Puig I, Domínguez D, Julien-Grille S, Guaita-Esteruelas S, Peiró S, Baulida J, Francí C, Dedhar S, Larue L, García de Herreros A (Sep 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, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (Aug 2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America 101 (33): 12130–5. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
• Kajita M, McClinic KN, Wade PA (Sep 2004). "Aberrant expression of the transcription factors snail and slug alters the response to genotoxic stress". Molecular and Cellular Biology 24 (17): 7559–66. doi:10.1128/MCB.24.17.7559-7566.2004. PMC 506998. PMID 15314165.
• Zhou BP, Deng J, Xia W, Xu J, Li YM, Gunduz M, Hung MC (Oct 2004). "Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial-mesenchymal transition". Nature Cell Biology 6 (10): 931–40. doi:10.1038/ncb1173. PMID 15448698.
• Saito T, Oda Y, Kawaguchi K, Sugimachi K, Yamamoto H, Tateishi N, Tanaka K, Matsuda S, Iwamoto Y, Ladanyi M, Tsuneyoshi M (Nov 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.