Transforming growth factor-beta 1 (TGF-beta 1) 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-beta 1-induced cell scattering, migration and invasion. Moreover, Q61LRac1 enhanced metalloproteinase-9 (MMP9) production to levels comparable to those induced by TGF-beta 1, while N17TRac1 was inhibitory. TGF-beta 1-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-beta 1-induced MMP9 expression and secretion in Q61LRac1 expressing cells. We propose that regulation of TGF-beta 1-mediated plasticity of transformed keratinocytes requires the cooperation between the... Rac1 and MAPK signalling pathways.
TY - JOUR
AU - Santibanez, Juan
AU - Krstić, Jelena
AU - Fabra, Angels
AU - Cano, Amparo
AU - Quintanilla, Miguel
PY - 2010
UR - http://rimi.imi.bg.ac.rs/handle/123456789/291
AB - Transforming growth factor-beta 1 (TGF-beta 1) 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-beta 1-induced cell scattering, migration and invasion. Moreover, Q61LRac1 enhanced metalloproteinase-9 (MMP9) production to levels comparable to those induced by TGF-beta 1, while N17TRac1 was inhibitory. TGF-beta 1-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-beta 1-induced MMP9 expression and secretion in Q61LRac1 expressing cells. We propose that regulation of TGF-beta 1-mediated plasticity of transformed keratinocytes requires the cooperation between the Rac1 and MAPK signalling pathways.
PB - Elsevier Science Bv, Amsterdam
T2 - FEBS Letters
T1 - Rac1 modulates TGF-beta 1-mediated epithelial cell plasticity and MMP9 production in transformed keratinocytes
EP - 2310
IS - 11
SP - 2305
VL - 584
DO - 10.1016/j.febslet.2010.03.042
UR - conv_2290
ER -
@article{
author = "Santibanez, Juan and Krstić, Jelena and Fabra, Angels and Cano, Amparo and Quintanilla, Miguel",
year = "2010",
abstract = "Transforming growth factor-beta 1 (TGF-beta 1) 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-beta 1-induced cell scattering, migration and invasion. Moreover, Q61LRac1 enhanced metalloproteinase-9 (MMP9) production to levels comparable to those induced by TGF-beta 1, while N17TRac1 was inhibitory. TGF-beta 1-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-beta 1-induced MMP9 expression and secretion in Q61LRac1 expressing cells. We propose that regulation of TGF-beta 1-mediated plasticity of transformed keratinocytes requires the cooperation between the Rac1 and MAPK signalling pathways.",
publisher = "Elsevier Science Bv, Amsterdam",
journal = "FEBS Letters",
title = "Rac1 modulates TGF-beta 1-mediated epithelial cell plasticity and MMP9 production in transformed keratinocytes",
pages = "2310-2305",
number = "11",
volume = "584",
doi = "10.1016/j.febslet.2010.03.042",
url = "conv_2290"
}
Santibanez, J., Krstić, J., Fabra, A., Cano, A.,& Quintanilla, M.. (2010). Rac1 modulates TGF-beta 1-mediated epithelial cell plasticity and MMP9 production in transformed keratinocytes. in FEBS Letters
Elsevier Science Bv, Amsterdam., 584(11), 2305-2310.
https://doi.org/10.1016/j.febslet.2010.03.042
conv_2290
Santibanez J, Krstić J, Fabra A, Cano A, Quintanilla M. Rac1 modulates TGF-beta 1-mediated epithelial cell plasticity and MMP9 production in transformed keratinocytes. in FEBS Letters. 2010;584(11):2305-2310.
doi:10.1016/j.febslet.2010.03.042
conv_2290 .
Santibanez, Juan, Krstić, Jelena, Fabra, Angels, Cano, Amparo, Quintanilla, Miguel, "Rac1 modulates TGF-beta 1-mediated epithelial cell plasticity and MMP9 production in transformed keratinocytes" in FEBS Letters, 584, no. 11 (2010):2305-2310,
https://doi.org/10.1016/j.febslet.2010.03.042 .,
conv_2290 .
