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SMAD3 is essential for transforming growth factor-beta 1-induced urokinase type plasminogen activator expression and migration in transformed keratinocytes
dc.creator | Krstić, Jelena | |
dc.creator | Bugarski, Diana | |
dc.creator | Santibanez, Juan F. | |
dc.date.accessioned | 2021-04-20T12:29:12Z | |
dc.date.available | 2021-04-20T12:29:12Z | |
dc.date.issued | 2012 | |
dc.identifier.issn | 0959-8049 | |
dc.identifier.uri | http://rimi.imi.bg.ac.rs/handle/123456789/415 | |
dc.description.abstract | Transforming growth factor-beta 1 (TGF-beta 1) stimulates the extracellular matrix degrading proteases expression and cell migration in order to enhance cancer cells malignancy. In the present study, we analysed the role of TGF-beta 1-induced Smad3 activation in the urokinase type plasminogen activator (uPA) production, as well as in cell migration and E-cadherin downregulation in transformed PDV keratinocyte cell line. TGF-beta 1 signalling was interfered by the chemical inhibitor of the TGF-beta 1-receptor 1 (ALK5), SB505124, and the specific Smad3 inhibitor, SiS3. Our results showed that TGF-beta 1 stimulates uPA expression directly through ALK5 activation. The inhibition of Smad3 strongly reduced the capacity of TGF-beta 1 to stimulate uPA expression, in parallel decreasing the uPA inhibitor plasminogen activator inhibitor type 1 (PAI-1) expression. In addition, the transient expression of dominant negative Smad3 mutant inhibited the TGF-beta 1-induced uPA promoter transactivation. Moreover, Smad3-/- mouse embryonic fibroblasts were refractory to the induction of uPA by TGF-beta 1. The inhibition of both ALK5 and Smad3 dramatically blocked the TGF-beta 1-stimulated E-cadherin downregulation, F-actin reorganisation and migration of PDV cells. Taken together, our results suggest that the TGF-beta 1-induced activation of Smad3 is the critical step for the uPA upregulation and E-cadherin downregulation, which are the key events preceding the induction of cell migration by TGF-beta 1 in transformed cells. | en |
dc.publisher | Elsevier Sci Ltd, Oxford | |
dc.relation | Chile Comision Nacional de Investigacion Cientifica y Tecnologica FONDECYT [1050476] | |
dc.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175062/RS// | |
dc.rights | openAccess | |
dc.source | European Journal of Cancer | |
dc.subject | TGF-beta 1 | en |
dc.subject | uPA | en |
dc.subject | PAI-1 | en |
dc.subject | Smad3 | en |
dc.subject | E-cadherin | en |
dc.subject | Migration | en |
dc.title | SMAD3 is essential for transforming growth factor-beta 1-induced urokinase type plasminogen activator expression and migration in transformed keratinocytes | en |
dc.type | article | |
dc.rights.license | ARR | |
dc.citation.epage | 1557 | |
dc.citation.issue | 10 | |
dc.citation.other | 48(10): 1550-1557 | |
dc.citation.rank | M21 | |
dc.citation.spage | 1550 | |
dc.citation.volume | 48 | |
dc.identifier.doi | 10.1016/j.ejca.2011.06.043 | |
dc.identifier.fulltext | http://rimi.imi.bg.ac.rs/bitstream/id/322/412.pdf | |
dc.identifier.pmid | 21798735 | |
dc.identifier.scopus | 2-s2.0-84862025999 | |
dc.identifier.wos | 000305278600016 | |
dc.type.version | publishedVersion |