Filamin a expression negatively regulates Sphingosine-1-phosphate-induced NF-κB activation in melanoma cells by inhibition o Akt signaling

Autores
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
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Campos, Ludmila Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Rodriguez, Yamila Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Machado Leopoldino, Andreia. Virginia Commonwealth University. School of Medicine; Estados Unidos. Universidade de Sao Paulo; Brasil
Fil: Hait, Nitai C.. Virginia Commonwealth University. School of Medicine; Estados Unidos
Fil: Lopez Bergami, Pablo Roberto. Universidad Maimonides; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Castro, Melina Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Sanchez, Emilse Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Maceyka, Michael. Virginia Commonwealth University. School of Medicine; Estados Unidos
Fil: Spiegel, Sarah. Virginia Commonwealth University School Of Medicine;
Fil: Alvarez, Sergio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Materia
FILAMIN A
SPHINGOSINE-1--PHOSPHATE RECEPTORS
CANCER
INFLAMATION
NF-κB ACTIVATION
AKT
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/14683
Acceder
id CONICETDig_e40c0d81c9edbbc4082962c9daf6f164
oai_identifier_str oai:ri.conicet.gov.ar:11336/14683
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Filamin a expression negatively regulates Sphingosine-1-phosphate-induced NF-κB activation in melanoma cells by inhibition o Akt signalingCampos, Ludmila EstefaníaRodriguez, Yamila IsabelMachado Leopoldino, AndreiaHait, Nitai C.Lopez Bergami, Pablo RobertoCastro, Melina GabrielaSanchez, Emilse SilvinaMaceyka, MichaelSpiegel, SarahAlvarez, Sergio EduardoFILAMIN ASPHINGOSINE-1--PHOSPHATE RECEPTORSCANCERINFLAMATIONNF-κB ACTIVATIONAKThttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Sphingosine-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.Fil: Campos, Ludmila Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Rodriguez, Yamila Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Machado Leopoldino, Andreia. Virginia Commonwealth University. School of Medicine; Estados Unidos. Universidade de Sao Paulo; BrasilFil: Hait, Nitai C.. Virginia Commonwealth University. School of Medicine; Estados UnidosFil: Lopez Bergami, Pablo Roberto. Universidad Maimonides; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Castro, Melina Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Sanchez, Emilse Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Maceyka, Michael. Virginia Commonwealth University. School of Medicine; Estados UnidosFil: Spiegel, Sarah. Virginia Commonwealth University School Of Medicine;Fil: Alvarez, Sergio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaAmerican Society for Microbiology2015-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/14683Campos, 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; 320-3290270-7306enginfo:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/10.1128/MCB.00554-15info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:00:21Zoai:ri.conicet.gov.ar:11336/14683instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:00:21.525CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Filamin a expression negatively regulates Sphingosine-1-phosphate-induced NF-κB activation in melanoma cells by inhibition o Akt signaling
title Filamin a expression negatively regulates Sphingosine-1-phosphate-induced NF-κB activation in melanoma cells by inhibition o Akt signaling
spellingShingle Filamin a expression negatively regulates Sphingosine-1-phosphate-induced NF-κB activation in melanoma cells by inhibition o Akt signaling
Campos, Ludmila Estefanía
FILAMIN A
SPHINGOSINE-1--PHOSPHATE RECEPTORS
CANCER
INFLAMATION
NF-κB ACTIVATION
AKT
title_short Filamin a expression negatively regulates Sphingosine-1-phosphate-induced NF-κB activation in melanoma cells by inhibition o Akt signaling
title_full Filamin a expression negatively regulates Sphingosine-1-phosphate-induced NF-κB activation in melanoma cells by inhibition o Akt signaling
title_fullStr Filamin a expression negatively regulates Sphingosine-1-phosphate-induced NF-κB activation in melanoma cells by inhibition o Akt signaling
title_full_unstemmed Filamin a expression negatively regulates Sphingosine-1-phosphate-induced NF-κB activation in melanoma cells by inhibition o Akt signaling
title_sort Filamin a expression negatively regulates Sphingosine-1-phosphate-induced NF-κB activation in melanoma cells by inhibition o Akt signaling
dc.creator.none.fl_str_mv 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
author Campos, Ludmila Estefanía
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv FILAMIN A
SPHINGOSINE-1--PHOSPHATE RECEPTORS
CANCER
INFLAMATION
NF-κB ACTIVATION
AKT
topic FILAMIN A
SPHINGOSINE-1--PHOSPHATE RECEPTORS
CANCER
INFLAMATION
NF-κB ACTIVATION
AKT
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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.
Fil: Campos, Ludmila Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Rodriguez, Yamila Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Machado Leopoldino, Andreia. Virginia Commonwealth University. School of Medicine; Estados Unidos. Universidade de Sao Paulo; Brasil
Fil: Hait, Nitai C.. Virginia Commonwealth University. School of Medicine; Estados Unidos
Fil: Lopez Bergami, Pablo Roberto. Universidad Maimonides; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Castro, Melina Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Sanchez, Emilse Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Maceyka, Michael. Virginia Commonwealth University. School of Medicine; Estados Unidos
Fil: Spiegel, Sarah. Virginia Commonwealth University School Of Medicine;
Fil: Alvarez, Sergio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
description 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.
publishDate 2015
dc.date.none.fl_str_mv 2015-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/14683
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
0270-7306
url http://hdl.handle.net/11336/14683
identifier_str_mv 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
0270-7306
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/
info:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/10.1128/MCB.00554-15
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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