Switching on-off Snail: LOXL2 versus GSK3beta.

Epithelial-mesenchymal transition (EMT) is considered as an essential determinant of carcinoma progression. The transcription factor Snail controls EMT by repressing E-cadherin gene expression and other epithelial genes. Snail protein stability and cellular localization is finely controlled by GSK3beta-dependent phosphorylation and subsequent ubiquitination. GSK3beta phosphorylates Snail at two different motifs which induce its nuclear export and association with beta-Trcp thus leading to Snail degradation. Recently, Snail was found to interact physical and functionally with LOXL2, a member of the lysyl oxidase gene family. Interestingly, LOXL2 seems to attenuate the GSK3beta-dependent Snail degradation. Here, we discuss the relevance of this new potential mechanism of regulation and the role of LOXL2 during carcinoma progression.