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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Santibáñez, JF; Kocić, J; Fabra, A; Cano, A; Quintanilla, M.
Rac1 modulates TGF-beta1-mediated epithelial cell plasticity and MMP9 production in transformed keratinocytes.
FEBS Lett. 2010; 584(11): 2305-2310.
Doi: 10.1016/j.febslet.2010.03.042
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- Co-authors Med Uni Graz
- Krstic Jelena
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- Abstract:
- Transforming growth factor-beta1 (TGF-beta1) 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-beta1-induced cell scattering, migration and invasion. Moreover, Q61LRac1 enhanced metalloproteinase-9 (MMP9) production to levels comparable to those induced by TGF-beta1, while N17TRac1 was inhibitory. TGF-beta1-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-beta1-induced MMP9 expression and secretion in Q61LRac1 expressing cells. We propose that regulation of TGF-beta1-mediated plasticity of transformed keratinocytes requires the cooperation between the Rac1 and MAPK signalling pathways. Copyright 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cadherins - metabolism
- Cell Dedifferentiation -
- Cell Movement -
- Enzyme Inhibitors - pharmacology
- Epithelial Cells - metabolism
- Flavonoids - pharmacology
- Keratinocytes - metabolism
- Matrix Metalloproteinase 9 - metabolism
- Mice -
- Mitogen-Activated Protein Kinases - metabolism
- Signal Transduction -
- Transforming Growth Factor beta1 - metabolism
- Find related publications in this database (Keywords)
- Keratinocyte
- Transforming growth factor-beta 1
- Metalloproteinase-9
- Rac1
- Snail1
- Mitogen-activated protein kinase
- Epithelial-mesenchymal transition
- Migration