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 GSK3β-dependent phosphorylation and subsequent ubiquitination. GSK3β phosphorylates Snail at two different motifs which induce its nuclear export and association with β-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 GSKSβ-dependent Snail degradation. Here, we discuss the relevance of this new potential mechanism of regulation and the role of LOXL2 during carcinoma progression. ©2005 Landes Bioscience.

Experimental work at A. Cano’s laboratory was supported by the Spanish Ministry of Education and Science (SAF04-00361) and Instituto de Salud Carlos III, RTICCC (FIS03 C03/10) to A.C. and F.P. H.P. was supported by a grant from Justesa Imagen, SA.

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