Rac1 modulates TGF-β1-mediated epithelial cell plasticity and MMP9 production in transformed keratinocytes

被引：42

作者：

Santibanez, Juan F. ^{[1
,2
]}

Kocic, Jelena ^{[1
]}

Fabra, Angels ^{[3
]}

Cano, Amparo ^{[4
]}

Quintanilla, Miguel ^{[4
]}

机构：

[1] Univ Belgrade, Inst Med Res IMI, Lab Expt Hematol, Belgrade 11129, Serbia

[2] Univ Chile, INTA, Lab Biol Celular, Santiago, Chile

[3] Ctr Mol Oncol, IDIBELL Inst Recerca Oncol, Barcelona, Spain

[4] Univ Autonoma Madrid, CSIC, Inst Invest Biomed Alberto Sols, Madrid, Spain

来源：

FEBS LETTERS | 2010年 / 584卷 / 11期

关键词：

Keratinocyte; Transforming growth factor-beta 1; Metalloproteinase-9; Rac1; Snail1; Mitogen-activated protein kinase; Epithelial-mesenchymal transition; Migration; RAS/MAPK SIGNALING PATHWAY; MESENCHYMAL TRANSITION; TGF-BETA; GROWTH FACTOR-BETA(1); INVASIVE PHENOTYPE; TUMOR-METASTASIS; SMALL GTPASES; RHO-GTPASES; EXPRESSION; PROGRESSION;

D O I：

10.1016/j.febslet.2010.03.042

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

引用

页码：2305 / 2310

页数：6

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