Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Villar, V; Kocić, J; Santibanez, JF.
Spred2 inhibits TGF-beta1-induced urokinase type plasminogen activator expression, cell motility and epithelial mesenchymal transition.
Int J Cancer. 2010; 127(1): 77-85.
Doi: 10.1002/ijc.25045
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-authors Med Uni Graz
- Krstic Jelena
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- TGF-beta1 is a potent inductor of malignance in cancer cells. TGF-beta1 stimulates the expression of extracellular matrix degrading proteases, cell migration and it is also involved in the epithelial-mesenchymal transition (EMT). In the present work, we analyzed the role of Spred2 in the urokinase-type plasminogen activator (uPA) stimulation, EMT and cell migration by TGF-beta1. We found that both the expression of mRNA and the protein level of Spred2 were lower in transformed keratinocytes PDV compared with immortalized keratinocytes MCA-3D. The transient ectopic expression of Spred2 in PDV cells inhibited the TGF-beta1-transactivated SRE-Luc reporter which is related with the ERK1,2 signal. The stable ectopic expression of Spred2 in PDV cells (SP cells) led to the loss of ERK 1,2 activation by TGF-beta1, although Smad2 activation was not affected, and the knockdown of Spred2 enhanced the activation of ERK1,2 signal by TGF-beta1. The increment of uPA expression induced by TGF-beta1 was suppressed in SP cells. In contrast, the stimulus on PAI-1 expression was not affected and comparable to parental PDV cells. SP cells under TGF-beta1 treatment were unable to display the EMT, since the overexpression of Spred2 abolished the TGF-beta1-induced disruption of the E-cadherin cell to cell interactions, reorganization of the actin cytoskeleton and upregulation of the mesenchymal marker vimentin. Finally, SP cells could not respond to the TGF-beta1 stimulus on cell migration. Taken together, the data in the present study suggests that Spred2 is a regulator of TGF-beta1-induced malignance in transformed keratinocytes.
- Find related publications in this database (using NLM MeSH Indexing)
- Base Sequence -
- Cell Movement - physiology
- DNA Primers -
- Enzyme Activation -
- Epithelial Cells - cytology
- Extracellular Signal-Regulated MAP Kinases - metabolism
- Fluorescent Antibody Technique -
- Gene Knockdown Techniques -
- Humans -
- Mesoderm - cytology
- Repressor Proteins - genetics
- Repressor Proteins - physiology
- Reverse Transcriptase Polymerase Chain Reaction -
- Transforming Growth Factor beta1 - physiology
- Urokinase-Type Plasminogen Activator - metabolism
- Find related publications in this database (Keywords)
- TGF-beta 1
- ERK 1,2
- Spred2
- u-PA
- EMT