Alpha-catulin down-regulates E-cadherin and promotes melanoma progression and invasion
International Journal of Cancer, 06/29/2012
Kreiseder B et al. – Consistent with the molecular changes,alpha-catulin provoked invasion of melanoma cells in a 3D culture assay by upregulation of the matrix metalloproteinases 2 and 9 and activation of ROCK/Rho. Alpha-catulin may represent a key driver of the metastatic process, implicating potential for therapeutic interference.Methods
- Alpha-Catulin (CTNNAL1) is a cytoplasmic molecule that integrates the crosstalk between NF-kappaB and Rho signalling pathways, binds to alpha-catenin and increases the level of both alpha-catenin and beta-catenin and has therefore potential effects on inflammation, apoptosis, and cytoskeletal reorganization.
- Alpha-catulin is highly expressed in melanoma cells.
- Expression of alpha-catulin promoted melanoma progression, and occurred concomitantly with the downregulation of E-cadherin and the upregulation of expression of mesenchymal genes such as N-cadherin, Snail/Slug and the matrix metalloproteinases 2 and 9.
- Knockdown of alpha-catulin promoted adhesion to, and inhibited migration away from keratinocytes in an E-cadherin-dependent manner, and decreased the transmigration through a keratinocyte monolayer, as well as in Transwell assays using collagens, laminin and fibronectin coating.
- Moreover, knockdown promoted homotypic spheroid formation and concomitantly increased E-cadherin expression along with down-regulation of transcription factors implicated in its repression (Snail/Slug, Twist, ZEB).