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Rac1 modulates TGF‐β1‐mediated epithelial cell plasticity and MMP9 production in transformed keratinocytes
Author(s) -
Santibáñez Juan F.,
Kocić Jelena,
Fabra Angels,
Cano Amparo,
Quintanilla Miguel
Publication year - 2010
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.2010.03.042
Subject(s) - rac1 , microbiology and biotechnology , mapk/erk pathway , transforming growth factor , mmp9 , signal transduction , chemistry , epithelial–mesenchymal transition , cell migration , rac gtp binding proteins , biology , downregulation and upregulation , cell , gene , biochemistry
Transforming growth factor‐β1 (TGF‐β1) activates Rac1 GTPase in mouse transformed keratinocytes. Expression of a constitutively active Q61LRac1 mutant induced an epithelial to mesenchymal transition (EMT) linked to stimulation of cell migration and invasion. On the contrary, expression of a dominant‐negative N17TRac1 abolished TGF‐β1‐induced cell scattering, migration and invasion. Moreover, Q61LRac1 enhanced metalloproteinase‐9 (MMP9) production to levels comparable to those induced by TGF‐β1, while N17TRac1 was inhibitory. TGF‐β1‐mediated EMT involves the expression of the E‐cadherin repressor Snail1, regulated by the Rac1 and mitogen‐activated protein kinase (MAPK) pathways. Furthermore, MMP9 production was MAPK‐dependent, as the MEK inhibitor PD98059 decreased TGF‐β1‐induced MMP9 expression and secretion in Q61LRac1 expressing cells. We propose that regulation of TGF‐β1‐mediated plasticity of transformed keratinocytes requires the cooperation between the Rac1 and MAPK signalling pathways.