2026-06-14T03:32:30Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/179632024-11-29T16:10:23Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Peinado, Hector
author
Quintanilla, Miguel
author
Cano, Amparo
2024-02-12T11:33:26Z
2024-02-12T11:33:26Z
2003-06-06
J Biol Chem . 2003 ;278(23):21113-23.
10.1074/jbc.M211304200
0021-9258
The Journal of biological chemistry
12665527
http://hdl.handle.net/20.500.12105/17963
The Snail transcription factor has been described recently as a strong repressor of E-cadherin in epithelial cell lines, where its stable expression leads to the loss of E-cadherin expression and induces epithelial-mesenchymal transitions and an invasive phenotype. The mechanisms regulating Snail expression in development and tumor progression are not yet known. We show here that transforming growth factor beta-1 (TGFbeta1) induces Snail expression in Madin-Darby canine kidney cells and triggers epithelial-mesenchymal transitions by a mechanism dependent on the MAPK signaling pathway. Furthermore, TGFbeta1 induces the activity of Snail promoter, whereas fibroblast growth factor-2 has a milder effect but cooperates with TGFbeta1 in the induction of Snail promoter. Interestingly, TGFbeta1-mediated induction of Snail promoter is blocked by a dominant negative form of H-Ras (N17Ras), whereas oncogenic H-Ras (V12Ras) induces Snail promoter activity and synergistically cooperates with TGFbeta1. The effects of TGFbeta1 on Snail promoter are dependent of MEK1/2 activity but are apparently independent of Smad4 activity. In addition, H-Ras-mediated induction of Snail promoter, alone or in the presence of TGFbeta1, depends on both MAPK and phosphatidylinositol 3-kinase activities. These data support that MAPK and phosphatidylinositol 3-kinase signaling pathways are implicated in TGFbeta1-mediated induction of Snail promoter, probably through Ras activation and its downstream effectors.
eng
Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions.
journal article
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URL
https://repisalud.isciii.es/bitstreams/f6a2d921-1960-4631-8b69-803d036d44f8/download
File
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application/pdf
TransformingGrowthFactor_2003.pdf
URL
https://repisalud.isciii.es/bitstreams/1965e838-22d8-4c59-a199-c4fb318bddc2/download
File
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text/plain
TransformingGrowthFactor_2003.pdf.txt