SNAI1

Snail family zinc finger 1
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsSNAI1 ; SLUGH2; SNA; SNAH; SNAIL; SNAIL1; dJ710H13.1
External IDsOMIM: 604238 MGI: 98330 HomoloGene: 4363 GeneCards: SNAI1 Gene
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez661520613
EnsemblENSG00000124216ENSMUSG00000042821
UniProtO95863Q02085
RefSeq (mRNA)NM_005985NM_011427
RefSeq (protein)NP_005976NP_035557
Location (UCSC)Chr 20:
48.6 – 48.61 Mb
Chr 2:
167.54 – 167.54 Mb
PubMed search

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

  1. 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. 2.0 2.1 "Entrez Gene: SNAI1 snail homolog 1 (Drosophila)".
  3. 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.
  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. 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.
  6. 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.
  7. 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.
  8. 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. 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