The human embryonic protein SNAI2, commonly known as SLUG, is a zinc finger transcriptional repressor which downregulates expression of E-cadherin in premigratory neural crest cells; thus, SNAI2 induces tightly bound epithelial cells to break into a loose mesenchymal phenotype, allowing gastrulation of mesoderm in the developing embryo. Structurally similar to anti-apoptotic Ces-1 in C. elegans, SLUG is a negative regulator of productive cell death in the developing embryo and adults.
Widely expressed in human tissues, SLUG is most notably absent in peripheral blood leukocytes, adult liver, and both fetal and adult brain tissues. SLUG plays a role in breast carcinoma as well as leukemia by downregulation of E-cadherin, which supports mesenchymal phenotype by shifting expression from a Type I to Type II cadherin profile. Maintenance of mesenchymal phenotype enables metastasis of tumor cells, though SLUG is expressed in carcinomas regardless to invasiveness. A knockout model using chick embryos has also showed inhibition of mesodermal and neural crest delamination; chick embryo Slug gain of function appears to increase neural crest production. Mutations in Slug are associated with loss of pregnancy during gastrulation in some animals.
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