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Spred2 inhibits TGF-beta 1-induced urokinase type plasminogen activator expression, cell motility and epithelial mesenchymal transition
dc.creator | Villar, Victor | |
dc.creator | Krstić, Jelena | |
dc.creator | Santibanez, Juan F. | |
dc.date.accessioned | 2021-04-20T12:20:34Z | |
dc.date.available | 2021-04-20T12:20:34Z | |
dc.date.issued | 2010 | |
dc.identifier.issn | 0020-7136 | |
dc.identifier.uri | http://rimi.imi.bg.ac.rs/handle/123456789/285 | |
dc.description.abstract | TGF-beta 1 is a potent inductor of malignance in cancer cells. TGF-beta 1 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-beta 1. 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-beta 1-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-beta 1, although Smad2 activation was not affected, and the knockdown of Spred2 enhanced the activation of ERK1,2 signal by TGF-beta 1. The increment of uPA expression induced by TGF-beta 1 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-beta 1 treatment were unable to display the EMT, since the overexpression of Spred2 abolished the TGF-beta 1-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-beta 1 stimulus on cell migration. Taken together, the data in the present study suggests that Spred2 is a regulator of TGF-beta 1-induced malignance in transformed keratinocytes. | en |
dc.publisher | Wiley, Hoboken | |
dc.relation | Fondo Nacional de Ciencia y Tecnologia (FONDECYT) [1050476] | |
dc.relation | info:eu-repo/grantAgreement/MESTD/MPN2006-2010/145048/RS// | |
dc.rights | openAccess | |
dc.source | International Journal of Cancer | |
dc.subject | TGF-beta 1 | en |
dc.subject | ERK 1,2 | en |
dc.subject | Spred2 | en |
dc.subject | u-PA | en |
dc.subject | EMT | en |
dc.title | Spred2 inhibits TGF-beta 1-induced urokinase type plasminogen activator expression, cell motility and epithelial mesenchymal transition | en |
dc.type | article | |
dc.rights.license | ARR | |
dc.citation.epage | 85 | |
dc.citation.issue | 1 | |
dc.citation.other | 127(1): 77-85 | |
dc.citation.rank | M21 | |
dc.citation.spage | 77 | |
dc.citation.volume | 127 | |
dc.identifier.doi | 10.1002/ijc.25045 | |
dc.identifier.fulltext | http://rimi.imi.bg.ac.rs/bitstream/id/230/282.pdf | |
dc.identifier.pmid | 19908229 | |
dc.identifier.scopus | 2-s2.0-77953467576 | |
dc.identifier.wos | 000278148800008 | |
dc.type.version | publishedVersion |