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SNAI2  -  snail homolog 2 (Drosophila)

Homo sapiens

 
 
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Disease relevance of SNAI2

 

High impact information on SNAI2

  • Control of cell behavior during vertebrate development by Slug, a zinc finger gene [6].
  • In presence of Ln-5, cells undergo partial EMT, Snail, and Slug are up-regulated, E-cadherin is down-regulated but cells do not scatter [7].
  • In such cells, beta-catenin signaling, ErbB-1/2 levels, and ERK activation were reduced and Slug was undetectable [8].
  • In human cancer, aberrant expression of Snail and/or Slug has been correlated with invasive growth potential, a property primarily attributed to their ability to directly repress transcription of genes whose products are involved in cell-cell adhesion, such as E-cadherin, occludin, and claudins [9].
  • Snail or Slug expression also promoted resistance to programmed cell death elicited by DNA damage [9].
 

Biological context of SNAI2

  • Phylogenetic analysis of human zinc finger proteins with SNAG domain revealed that SNAI1, SNAI2 and SNAI3 were more closely related [10].
  • Comparative genomics on SNAI1, SNAI2, and SNAI3 orthologs [1].
  • Thus, aberrant expression of Snail or Slug may promote tumorigenesis through increased resistance to programmed cell death [9].
  • When we compared gene expression profiles between five MM cells and their multidrug-resistant (MM DX) sublines, we found that MM DX cells expressed both SCF and c-Kit and had higher mRNA levels of Slug [11].
  • Transfection of c-Kit in parental MM cells in the presence of SCF up-regulated Slug and increased resistance to the chemotherapeutic agents [11].
 

Anatomical context of SNAI2

  • SNAI2 induces the first phase of EMT, including desmosome dissociation, cell spreading, and initiation of cell separation [1].
  • To investigate the molecular mechanisms of alterations in epithelial cell fate mediated by aberrant expression of Snail or Slug, we analyzed the consequences of exogenous expression of these factors in human cancer cells [9].
  • Here, we identified a pathway that involves stem cell factor (SCF)/c-Kit/Slug in mediating multidrug resistance of MM cells [11].
  • We do, however, find that activation of Slug results in a significant reduction in keratinocyte proliferation [12].
  • They emphasize a link between Snail, Slug, and lymph node metastasis in a large sampling of mammary carcinomas, and suggest a role for Slug in the maintenance of semidifferentiated structures [13].
 

Associations of SNAI2 with chemical compounds

  • Knockdown of c-Kit or Slug expression with their respective small interfering RNA sensitized MM DX cells to the induction of apoptosis by different chemotherapeutic agents, including doxorubicin, paclitaxel, and vincristine [11].
  • Microarray analysis revealed that several genes, including Slug, were down-regulated by imatinib mesylate [14].
 

Physical interactions of SNAI2

 

Co-localisations of SNAI2

 

Regulatory relationships of SNAI2

  • The transient activation of c-Src is involved in cytoskeleton remodeling whereas the Ras pathway controls the transcription of genes such as the transcription factor Slug which is involved in the internalization of desmosomes [17].
  • In addition, Snail and Slug are able to effectively repress human Claudin-1-driven reporter gene constructs containing the wild-type promoter sequence, but not those with mutations in two proximal E-box elements [16].
 

Other interactions of SNAI2

 

Analytical, diagnostic and therapeutic context of SNAI2

References

  1. Comparative genomics on SNAI1, SNAI2, and SNAI3 orthologs. Katoh, M., Katoh, M. Oncol. Rep. (2005) [Pubmed]
  2. Slug is overexpressed in gastric carcinomas and may act synergistically with SIP1 and Snail in the down-regulation of E-cadherin. Alves, C.C., Rosivatz, E., Schott, C., Hollweck, R., Becker, I., Sarbia, M., Carneiro, F., Becker, K.F. J. Pathol. (2007) [Pubmed]
  3. Human transcription factor SLUG: mutation analysis in patients with neural tube defects and identification of a missense mutation (D119E) in the Slug subfamily-defining region. Stegmann, K., Boecker, J., Kosan, C., Ermert, A., Kunz, J., Koch, M.C. Mutat. Res. (1999) [Pubmed]
  4. SLUG in cancer development. Pérez-Mancera, P.A., González-Herrero, I., Pérez-Caro, M., Gutiérrez-Cianca, N., Flores, T., Gutiérrez-Adán, A., Pintado, B., Sánchez-Martín, M., Sánchez-García, I. Oncogene (2005) [Pubmed]
  5. SLUG (SNAI2) overexpression in embryonic development. Pérez-Mancera, P.A., González-Herrero, I., Maclean, K., Turner, A.M., Yip, M.Y., Sánchez-Martín, M., García, J.L., Robledo, C., Flores, T., Gutiérrez-Adán, A., Pintado, B., Sánchez-García, I. Cytogenet. Genome Res. (2006) [Pubmed]
  6. Control of cell behavior during vertebrate development by Slug, a zinc finger gene. Nieto, M.A., Sargent, M.G., Wilkinson, D.G., Cooke, J. Science (1994) [Pubmed]
  7. Laminin-5 with transforming growth factor-beta1 induces epithelial to mesenchymal transition in hepatocellular carcinoma. Giannelli, G., Bergamini, C., Fransvea, E., Sgarra, C., Antonaci, S. Gastroenterology (2005) [Pubmed]
  8. Autoregulation of E-cadherin expression by cadherin-cadherin interactions: the roles of beta-catenin signaling, Slug, and MAPK. Conacci-Sorrell, M., Simcha, I., Ben-Yedidia, T., Blechman, J., Savagner, P., Ben-Ze'ev, A. J. Cell Biol. (2003) [Pubmed]
  9. Aberrant expression of the transcription factors snail and slug alters the response to genotoxic stress. Kajita, M., McClinic, K.N., Wade, P.A. Mol. Cell. Biol. (2004) [Pubmed]
  10. Identification and characterization of human SNAIL3 (SNAI3) gene in silico. Katoh, M., Katoh, M. Int. J. Mol. Med. (2003) [Pubmed]
  11. Induction of stem cell factor/c-Kit/slug signal transduction in multidrug-resistant malignant mesothelioma cells. Catalano, A., Rodilossi, S., Rippo, M.R., Caprari, P., Procopio, A. J. Biol. Chem. (2004) [Pubmed]
  12. Slug regulates integrin expression and cell proliferation in human epidermal keratinocytes. Turner, F.E., Broad, S., Khanim, F.L., Jeanes, A., Talma, S., Hughes, S., Tselepis, C., Hotchin, N.A. J. Biol. Chem. (2006) [Pubmed]
  13. Snail and slug play distinct roles during breast carcinoma progression. C??me, C., Magnino, F., Bibeau, F., De Santa Barbara, P., Becker, K.F., Theillet, C., Savagner, P. Clin. Cancer Res. (2006) [Pubmed]
  14. Slug (SNAI2) down-regulation by RNA interference facilitates apoptosis and inhibits invasive growth in neuroblastoma preclinical models. Vitali, R., Mancini, C., Cesi, V., Tanno, B., Mancuso, M., Bossi, G., Zhang, Y., Martinez, R.V., Calabretta, B., Dominici, C., Raschellà, G. Clin. Cancer Res. (2008) [Pubmed]
  15. Human SLUG does not directly bind to CtBP1. Bailey, C.K., Misra, S., Mittal, M.K., Chaudhuri, G. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  16. The transcription factors Slug and Snail act as repressors of Claudin-1 expression in epithelial cells. Martínez-Estrada, O.M., Cullerés, A., Soriano, F.X., Peinado, H., Bolós, V., Martínez, F.O., Reina, M., Cano, A., Fabre, M., Vilaró, S. Biochem. J. (2006) [Pubmed]
  17. Epithelial cell plasticity in development and tumor progression. Thiery, J.P., Chopin, D. Cancer Metastasis Rev. (1999) [Pubmed]
  18. Slug Expression in the E-cadherin preserved tumors is related to prognosis in patients with esophageal squamous cell carcinoma. Uchikado, Y., Natsugoe, S., Okumura, H., Setoyama, T., Matsumoto, M., Ishigami, S., Aikou, T. Clin. Cancer Res. (2005) [Pubmed]
  19. Vascular endothelial growth factor receptor-1 activation mediates epithelial to mesenchymal transition in human pancreatic carcinoma cells. Yang, A.D., Camp, E.R., Fan, F., Shen, L., Gray, M.J., Liu, W., Somcio, R., Bauer, T.W., Wu, Y., Hicklin, D.J., Ellis, L.M. Cancer Res. (2006) [Pubmed]
  20. Snail, Slug, and Smad-interacting protein 1 as novel parameters of disease aggressiveness in metastatic ovarian and breast carcinoma. Elloul, S., Elstrand, M.B., Nesland, J.M., Tropé, C.G., Kvalheim, G., Goldberg, I., Reich, R., Davidson, B. Cancer (2005) [Pubmed]
  21. Deletion of the SLUG (SNAI2) gene results in human piebaldism. Sánchez-Martín, M., Pérez-Losada, J., Rodríguez-García, A., González-Sánchez, B., Korf, B.R., Kuster, W., Moss, C., Spritz, R.A., Sánchez-García, I. Am. J. Med. Genet. A (2003) [Pubmed]
  22. Expression of the transcription factors snail, slug, and twist and their clinical significance in human breast cancer. Martin, T.A., Goyal, A., Watkins, G., Jiang, W.G. Ann. Surg. Oncol. (2005) [Pubmed]
  23. Zinc finger transcription factor Slug is a novel target gene of aryl hydrocarbon receptor. Ikuta, T., Kawajiri, K. Exp. Cell Res. (2006) [Pubmed]
 
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