Artículo
Filamin a expression negatively regulates Sphingosine-1-phosphate-induced NF-κB activation in melanoma cells by inhibition o Akt signaling
Campos, Ludmila Estefanía
; Rodriguez, Yamila Isabel
; Machado Leopoldino, Andreia; Hait, Nitai C.; Lopez Bergami, Pablo Roberto
; Castro, Melina Gabriela
; Sanchez, Emilse Silvina
; Maceyka, Michael; Spiegel, Sarah; Alvarez, Sergio Eduardo
Fecha de publicación:
11/2015
Editorial:
American Society for Microbiology
Revista:
Molecular and Cellular Biology
ISSN:
0270-7306
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator that regulates many processes in inflammation and cancer. S1P is a ligand for five G-protein-coupled receptors, S1PR1 to -5, and also has important intracellular actions. Previously, we showed that intracellular S1P is involved in tumor necrosis factor alpha (TNF)-induced NF-κB activation in melanoma cell lines that express filamin A (FLNA). Here, we show that extracellular S1P activates NF-κB only in melanoma cells that lack FLNA. In these cells, S1P, but not TNF, promotes IκB kinase (IKK) and p65 phosphorylation, IκBα degradation, p65 nuclear translocation, and NF-κB reporter activity. NF-κB activation induced by S1P was mediated via S1PR1 and S1PR2. Exogenous S1P enhanced the phosphorylation of protein kinase Cδ (PKCδ), and its downregulation reduced S1P-induced the phosphorylation of IKK and p65. In addition, silencing of Bcl10 also inhibited S1P-induced IKK phosphorylation. Surprisingly, S1P reduced Akt activation in melanoma cells that express FLNA, whereas in the absence of FLNA, high phosphorylation levels of Akt were maintained, enabling S1P-mediated NF-κB signaling. In accord, inhibition of Akt suppressed S1P-mediated IKK and p65 phosphorylation and degradation of IκBα. Hence, these results support a negative role of FLNA in S1P-mediated NF-κB activation in melanoma cells through modulation of Akt.
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Articulos(IMIBIO-SL)
Articulos de INST. MULTIDICIPLINARIO DE INV. BIO. DE SAN LUIS
Articulos de INST. MULTIDICIPLINARIO DE INV. BIO. DE SAN LUIS
Citación
Campos, Ludmila Estefanía; Rodriguez, Yamila Isabel; Machado Leopoldino, Andreia; Hait, Nitai C.; Lopez Bergami, Pablo Roberto; et al.; Filamin a expression negatively regulates Sphingosine-1-phosphate-induced NF-κB activation in melanoma cells by inhibition o Akt signaling; American Society for Microbiology; Molecular and Cellular Biology; 36; 2; 11-2015; 320-329
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