Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/17961
Title
A molecular role for lysyl oxidase-like 2 enzyme in snail regulation and tumor progression.
Author(s)
Date issued
2005-10-05
Citation
EMBO J . 2005 ;24(19):3446-58
Language
Inglés
Document type
journal article
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.
MESH
Gene Expression Regulation | Amino Acid Oxidoreductases | Animals | Blotting, Western | Cadherins | Carcinoma | Cell Line, Tumor | DNA Primers | Epithelial Cells | Fluorescent Antibody Technique | Humans | Immunoprecipitation | In Situ Nick-End Labeling | Mice | RNA Interference | Reverse Transcriptase Polymerase Chain Reaction | Snail Family Transcription Factors | Transcription Factors | Transfection
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