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Closed Access item A molecular role for lysyl oxidase-like 2 enzyme in Snail regulation and tumor progression

Authors:Peinado, Héctor
Iglesias de la Cruz, Carmen
Olmeda, David
Vega, Sonia
Nieto, M. Ángela
Cano, Amparo
Portillo, Francisco
Keywords:E-cadherin, EMT, LOXL, Snail, Tumor progression
Issue Date:2005
Publisher:Nature Publishing Group
Citation:Embo Journal 24(19): 3446-3458 (2005)
Abstract:The transcription factor Snail controls epithelial–mesenchymal transitions (EMT) by repressing E-cadherin expression and other epithelial genes. However, the mechanisms involved in the regulation of Snail function are not fully understood. Here we show that lysyl-oxidase-like 2 and 3 (LOXL2 and LOXL3), two members of the lysyl-oxidase gene family, interact and cooperate with Snail to downregulate E-cadherin expression. Snail's lysine residues 98 and 137 are essential for Snail stability, functional cooperation with LOXL2/3 and induction of EMT. Overexpression of LOXL2 or LOXL3 in epithelial cells induces an EMT process, supporting their implication in tumor progression. The biological importance of LOXL2 is further supported by RNA interference of LOXL2 in Snail-expressing metastatic carcinoma cells, which led to a strong decrease of tumor growth associated to increased apoptosis and reduced expression of mesenchymal and invasive/angiogenic markers. Taken together, these results establish a direct link between LOXL2 and Snail in carcinoma progression.
Description:13 páginas, 9 figuras.-- et al.
Publisher version (URL):http://dx.doi.org/10.1038/sj.emboj.7600781
URI:http://hdl.handle.net/10261/32365
ISSN:0261-4189
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