engleski

Crosstalk between urokinase system and TGFβ pathway in human glioblastoma cell line

Transforming growth factor β (TGFβ) pathway is one of the most important signaling pathways in differentiation and cell reprogramming. Its main role is mediation in proliferation arrest and tumor suppression, but, on the other side, TGFβ can also regulate migration, angiogenesis and cell invasiveness, through epithelial-mesenchymal transition. The latter is a process of reprogramming by which cells of epithelial phenotype obtain mesenchymal characteristics, including the production of extracellular matrix components and secretion of extracellular proteases. One of the extracellular protease systems is urokinase plasminogen activation system. Urokinase converts plasminogen into plasmin, a protease able to degrade and remodel extracellular matrix. Plasminogen activation is regulated on the transcription level of urokinase, its inhibitors PAI1 and PAI2, synthesis and degradation of their proteins. The aim was to analyze the effect of TGFβ on urokinase system of plasminogen activation in a glioblastoma cell line. TGFβ overexpression was obtained by transfection of the plasmid with TGFβ sequence. Transfected cells had increased urokinase activity. We analyzed changes in gene expression in a set of genes regulating urokinase activity, genes involved in TGFβ pathway, master transcription genes of epithelial-mesenchymal transition, as well as changes on the protein level, cell migration, and proliferation. We concluded that TGFβ modulates urokinase plasminogen activation system.

TGFβ, urokinase plasminogen activator, epithelial-mesenchymal transition, glioblastoma

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