Fig. 4. Downstream targets of Snail. Snail gene expression induces the loss of epithelial markers and the gain of mesenchymal markers, as well as inducing changes in cell shape, and changes related to morphology and to the acquisition of motility and invasive properties. The Snail genes also regulate cell proliferation and cell death. Not all of these targets are directly regulated by Snail genes: because Snail genes function as repressors, from Drosophila to humans (reviewed by Nieto, 2002), target upregulation might be due to the Snail-mediated repression of a repressor. However, their role as activators cannot be excluded. The molecules and processes shown in red are downregulated or impaired by Snail, and those in green are upregulated or promoted by Snail. BID, Bcl-interacting death agonist; CDK, cyclin-dependent kinase; DFF, DNA fragmentation factor; ERKs, extracellular signal-regulated kinases; MMPs, metalloproteinases; PI3K, phosphoinositide 3-kinase; p21, cyclin-dependent kinase inhibitor; p53, tumour suppressor; Rb, retinoblastoma; XR11, Xenopus Bcl-xL homologue.