Switching On-Off Snail: LOXL2 Versus GSK3?

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Abstract
Epithelial-mesenchymal transition (EMT) is considered as an essential determinant of carcinoma progression. The transcription factor Snail controls EMT by repressing Ecadherin gene expression and other epithelial genes. Snail protein stability and cellular localization is finely controlled by GSK3?-dependent phosphorylation and subsequent ubiquitination. GSK3? phosphorylates Snail at two different motifs which induce its nuclear export and association with ?-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 GSK3?- dependent Snail degradation. Here, we discuss the relevance of this new potential mechanism of regulation and the role of LOXL2 during carcinoma progression.

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