scholarly journals Transforming growth factor-β, matrix metalloproteinases, and urokinase-type plasminogen activator interaction in the cancer epithelial to mesenchymal transition

2017 ◽  
Vol 247 (3) ◽  
pp. 382-395 ◽  
Author(s):  
Juan F. Santibanez ◽  
Hristina Obradović ◽  
Tamara Kukolj ◽  
Jelena Krstić
Keyword(s):  
Growth Factor ◽  
Matrix Metalloproteinases ◽  
Plasminogen Activator ◽  
Epithelial To Mesenchymal Transition ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Mesenchymal Transition ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator

Modulation of Urokinase-Type Plasminogen Activator by Transforming Growth Factor β1 in Acetaldehyde-Activated Hepatic Stellate Cells

Pharmacology ◽  
2004 ◽  
Vol 73 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Georgina Pérez-Liz ◽  
Jorge Flores-Hernández ◽  
José-Antonio Arias-Montaño ◽  
Jorge-Alberto Reyes-Esparza ◽  
Lourdes Rodríguez-Fragoso
Keyword(s):  
Growth Factor ◽  
Plasminogen Activator ◽  
Hepatic Stellate Cells ◽  
Transforming Growth Factor ◽  
Stellate Cells ◽  
Transforming Growth Factor Β ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Activated Hepatic Stellate Cells

scholarly journals Transforming Growth Factor β/NR4A1-Inducible Breast Cancer Cell Migration and Epithelial-to-Mesenchymal Transition Is p38α (Mitogen-Activated Protein Kinase 14) Dependent

2017 ◽  
Vol 37 (18) ◽  
Author(s):  
Erik Hedrick ◽  
Stephen Safe
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Growth Factor ◽  
Nuclear Export ◽  
Epithelial To Mesenchymal Transition ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Mitogen Activated Protein Kinase ◽  
Mesenchymal Transition ◽  
Mitogen Activated Protein

ABSTRACT Transforming growth factor β (TGF-β)-induced migration of triple-negative breast cancer (TNBC) cells is dependent on nuclear export of the orphan receptor NR4A1, which plays a role in proteasome-dependent degradation of SMAD7. In this study, we show that TGF-β induces p38α (mitogen-activated protein kinase 14 [MAPK14]), which in turn phosphorylates NR4A1, resulting in nuclear export of the receptor. TGF-β/p38α and NR4A1 also play essential roles in the induction of epithelial-to-mesenchymal transition (EMT) and induction of β-catenin in TNBC cells, and these TGF-β-induced responses and nuclear export of NR4A1 are blocked by NR4A1 antagonists, the p38 inhibitor SB202190, and kinase-dead [p38(KD)] and dominant-negative [p38(DN)] forms of p38α. Inhibition of NR4A1 nuclear export results in nuclear export of TGF-β-induced β-catenin, which then undergoes proteasome-dependent degradation. TGF-β-induced β-catenin also regulates NR4A1 expression through formation of the β-catenin–TCF-3/TCF-4/LEF-1 complex on the NR4A1 promoter. Thus, TGF-β-induced nuclear export of NR4A1 in TNBC cells plays an essential role in cell migration, SMAD7 degradation, EMT, and induction of β-catenin, and all of these pathways are inhibited by bis-indole-derived NR4A1 antagonists that inhibit nuclear export of the receptor and thereby block TGF-β-induced migration and EMT.

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