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JNK mediates TGF‐β1‐induced epithelial mesenchymal transdifferentiation of mouse transformed keratinocytes
Author(s) -
Santibañez Juan F.
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.09.003
Subject(s) - transdifferentiation , fibronectin , microbiology and biotechnology , phosphorylation , kinase , c jun , chemistry , vimentin , transactivation , epithelial–mesenchymal transition , activator (genetics) , cancer research , biology , downregulation and upregulation , transcription factor , immunology , extracellular matrix , stem cell , biochemistry , immunohistochemistry , gene
In this study we analyzed the role of the c‐Jun N‐terminal kinases (JNK) pathway in the TGF‐β1 stimulation of urokinase‐type plasminogen activator (uPA), initial stages of epithelial‐mesenchymal transdifferentiation (EMT) and cell migration. TGF‐β1 induces JNK phosphorylation, c‐Jun transactivation and AP1 activation. The involvement of JNK was evaluated using dominant negative mutants SEK‐1 AL, JNK and cJun, depletion of JNK1,2 proteins by treatment of cells with antisense oligonucleotides, as well as the chemical inhibitor SP600125. Our results demonstrated that the JNK pathway is required in the TGF‐β1 enhancement of uPA, fibronectin, E‐cadherin delocalization, actin re‐organization and vimentin expression, concomitant with the induction of cell migration. These results allow us to suggest a role of JNK in the TGF‐β1 induction of EMT in relation with the stimulation of malignant properties of mouse transformed keratinocytes.