Wnt, hedgehog and snail: sister pathways that control by GSK-3beta and beta-Trcp in the regulation of metastasis.

The epithelial-mesenchymal transition have begun to attracted many attentions as a potential mechanism for metastasis. The phenotypic changes of increased motility and invasiveness of cancer cells are reminiscent of epithelial-mesenchymal transition (EMT) that associates with the downregulation of E-cadherin. Snail, zinc finger transcription factor, triggers this process by repressing E-cadherin expression. Recently Snail was found to be dually regulated GSK-3beta through protein stability and cellular localization. The involvement of GSK-3beta and beta-Trcp in the regulation of Snail is particular interesting, because these two molecules are also known to involve in the regulation of Wnt and hedgehog pathways that are known to control cell fate and morphogenesis during development and tumorigenesis. Here, we briefly compare these pathways and propose the possibility of cross-talk among these pathways in the regulation of cell adhesion, cell fate, and migration during metastasis.