KSHV-induced ligand mediated activation of PDGF receptor-alpha drives Kaposi's sarcomagenesis

Autores
Cavallin, Lucas E.; Ma, Qi; Naipauer, Julian; Gupta, Sachin; Kurian, Mani; Locatelli, Paola; Romanelli, Paolo; Nadji, Mehrdad; Goldschmidt Clermont, Pascal J.; Mesri, Enrique Alfredo
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Kaposi’s sarcoma (KS) herpesvirus (KSHV) causes KS, an angiogenic AIDS-associated spindle-cell neoplasm, by activating host oncogenic signaling cascades through autocrine and paracrine mechanisms. Tyrosine kinase receptor (RTK) proteomic arrays, identified PDGF receptor-alpha (PDGFRA) as the predominantly-activated RTK in KSHV-induced mouse KS-tumors. We show that: 1) KSHV lytic replication and the vGPCR can activate PDGFRA through upregulation of its ligands PDGFA/B, which increase c-myc, VEGF and KSHV gene expression in infected cells 2) KSHV infected spindle cells of most AIDS-KS lesions display robust phospho-PDGFRA staining 3) blocking PDGFRA-signaling with N-acetyl-cysteine, RTK-inhibitors Imatinib and Sunitinib, or dominant-negative PDGFRA inhibits tumorigenesis 4) PDGFRA D842V activating-mutation confers resistance to Imatinib in mouse-KS tumorigenesis. Our data show that KSHV usurps sarcomagenic PDGFRA signaling to drive KS. This and the fact that PDGFRA drives non-viral sarcomas highlights the importance for KSHV-induced ligand-mediated activation of PDGFRA in KS sarcomagenesis and shows that this oncogenic axis could be successfully blocked to impede KS tumor growth.
Fil: Cavallin, Lucas E.. University of Miami; Estados Unidos
Fil: Ma, Qi. University of Miami; Estados Unidos
Fil: Naipauer, Julian. University of Miami; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina
Fil: Gupta, Sachin. University of Miami; Estados Unidos
Fil: Kurian, Mani. University of Miami; Estados Unidos
Fil: Locatelli, Paola. University of Miami; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina
Fil: Romanelli, Paolo. University of Miami; Estados Unidos
Fil: Nadji, Mehrdad. University of Miami; Estados Unidos
Fil: Goldschmidt Clermont, Pascal J.. University of Miami; Estados Unidos
Fil: Mesri, Enrique Alfredo. University of Miami; Estados Unidos
Materia
AIDS-KS
KSHV
PDGFRA
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:11336/87756
Acceder
id CONICETDig_26b882e67f3ec8941741d63491bb96b5
oai_identifier_str oai:ri.conicet.gov.ar:11336/87756
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling KSHV-induced ligand mediated activation of PDGF receptor-alpha drives Kaposi's sarcomagenesisCavallin, Lucas E.Ma, QiNaipauer, JulianGupta, SachinKurian, ManiLocatelli, PaolaRomanelli, PaoloNadji, MehrdadGoldschmidt Clermont, Pascal J.Mesri, Enrique AlfredoAIDS-KSKSHVPDGFRAhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Kaposi’s sarcoma (KS) herpesvirus (KSHV) causes KS, an angiogenic AIDS-associated spindle-cell neoplasm, by activating host oncogenic signaling cascades through autocrine and paracrine mechanisms. Tyrosine kinase receptor (RTK) proteomic arrays, identified PDGF receptor-alpha (PDGFRA) as the predominantly-activated RTK in KSHV-induced mouse KS-tumors. We show that: 1) KSHV lytic replication and the vGPCR can activate PDGFRA through upregulation of its ligands PDGFA/B, which increase c-myc, VEGF and KSHV gene expression in infected cells 2) KSHV infected spindle cells of most AIDS-KS lesions display robust phospho-PDGFRA staining 3) blocking PDGFRA-signaling with N-acetyl-cysteine, RTK-inhibitors Imatinib and Sunitinib, or dominant-negative PDGFRA inhibits tumorigenesis 4) PDGFRA D842V activating-mutation confers resistance to Imatinib in mouse-KS tumorigenesis. Our data show that KSHV usurps sarcomagenic PDGFRA signaling to drive KS. This and the fact that PDGFRA drives non-viral sarcomas highlights the importance for KSHV-induced ligand-mediated activation of PDGFRA in KS sarcomagenesis and shows that this oncogenic axis could be successfully blocked to impede KS tumor growth.Fil: Cavallin, Lucas E.. University of Miami; Estados UnidosFil: Ma, Qi. University of Miami; Estados UnidosFil: Naipauer, Julian. University of Miami; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Gupta, Sachin. University of Miami; Estados UnidosFil: Kurian, Mani. University of Miami; Estados UnidosFil: Locatelli, Paola. University of Miami; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Romanelli, Paolo. University of Miami; Estados UnidosFil: Nadji, Mehrdad. University of Miami; Estados UnidosFil: Goldschmidt Clermont, Pascal J.. University of Miami; Estados UnidosFil: Mesri, Enrique Alfredo. University of Miami; Estados UnidosPublic Library of Science2018-07info: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/11336/87756Cavallin, Lucas E.; Ma, Qi; Naipauer, Julian; Gupta, Sachin; Kurian, Mani; et al.; KSHV-induced ligand mediated activation of PDGF receptor-alpha drives Kaposi's sarcomagenesis; Public Library of Science; Plos Pathogens; 14; 7; 7-2018; 1-281553-7366CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.ppat.1007175info:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007175info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:49:13Zoai:ri.conicet.gov.ar:11336/87756instacron: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 09:49:14.314CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv KSHV-induced ligand mediated activation of PDGF receptor-alpha drives Kaposi's sarcomagenesis
title KSHV-induced ligand mediated activation of PDGF receptor-alpha drives Kaposi's sarcomagenesis
spellingShingle KSHV-induced ligand mediated activation of PDGF receptor-alpha drives Kaposi's sarcomagenesis
Cavallin, Lucas E.
AIDS-KS
KSHV
PDGFRA
title_short KSHV-induced ligand mediated activation of PDGF receptor-alpha drives Kaposi's sarcomagenesis
title_full KSHV-induced ligand mediated activation of PDGF receptor-alpha drives Kaposi's sarcomagenesis
title_fullStr KSHV-induced ligand mediated activation of PDGF receptor-alpha drives Kaposi's sarcomagenesis
title_full_unstemmed KSHV-induced ligand mediated activation of PDGF receptor-alpha drives Kaposi's sarcomagenesis
title_sort KSHV-induced ligand mediated activation of PDGF receptor-alpha drives Kaposi's sarcomagenesis
dc.creator.none.fl_str_mv Cavallin, Lucas E.
Ma, Qi
Naipauer, Julian
Gupta, Sachin
Kurian, Mani
Locatelli, Paola
Romanelli, Paolo
Nadji, Mehrdad
Goldschmidt Clermont, Pascal J.
Mesri, Enrique Alfredo
author Cavallin, Lucas E.
author_facet Cavallin, Lucas E.
Ma, Qi
Naipauer, Julian
Gupta, Sachin
Kurian, Mani
Locatelli, Paola
Romanelli, Paolo
Nadji, Mehrdad
Goldschmidt Clermont, Pascal J.
Mesri, Enrique Alfredo
author_role author
author2 Ma, Qi
Naipauer, Julian
Gupta, Sachin
Kurian, Mani
Locatelli, Paola
Romanelli, Paolo
Nadji, Mehrdad
Goldschmidt Clermont, Pascal J.
Mesri, Enrique Alfredo
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv AIDS-KS
KSHV
PDGFRA
topic AIDS-KS
KSHV
PDGFRA
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Kaposi’s sarcoma (KS) herpesvirus (KSHV) causes KS, an angiogenic AIDS-associated spindle-cell neoplasm, by activating host oncogenic signaling cascades through autocrine and paracrine mechanisms. Tyrosine kinase receptor (RTK) proteomic arrays, identified PDGF receptor-alpha (PDGFRA) as the predominantly-activated RTK in KSHV-induced mouse KS-tumors. We show that: 1) KSHV lytic replication and the vGPCR can activate PDGFRA through upregulation of its ligands PDGFA/B, which increase c-myc, VEGF and KSHV gene expression in infected cells 2) KSHV infected spindle cells of most AIDS-KS lesions display robust phospho-PDGFRA staining 3) blocking PDGFRA-signaling with N-acetyl-cysteine, RTK-inhibitors Imatinib and Sunitinib, or dominant-negative PDGFRA inhibits tumorigenesis 4) PDGFRA D842V activating-mutation confers resistance to Imatinib in mouse-KS tumorigenesis. Our data show that KSHV usurps sarcomagenic PDGFRA signaling to drive KS. This and the fact that PDGFRA drives non-viral sarcomas highlights the importance for KSHV-induced ligand-mediated activation of PDGFRA in KS sarcomagenesis and shows that this oncogenic axis could be successfully blocked to impede KS tumor growth.
Fil: Cavallin, Lucas E.. University of Miami; Estados Unidos
Fil: Ma, Qi. University of Miami; Estados Unidos
Fil: Naipauer, Julian. University of Miami; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina
Fil: Gupta, Sachin. University of Miami; Estados Unidos
Fil: Kurian, Mani. University of Miami; Estados Unidos
Fil: Locatelli, Paola. University of Miami; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina
Fil: Romanelli, Paolo. University of Miami; Estados Unidos
Fil: Nadji, Mehrdad. University of Miami; Estados Unidos
Fil: Goldschmidt Clermont, Pascal J.. University of Miami; Estados Unidos
Fil: Mesri, Enrique Alfredo. University of Miami; Estados Unidos
description Kaposi’s sarcoma (KS) herpesvirus (KSHV) causes KS, an angiogenic AIDS-associated spindle-cell neoplasm, by activating host oncogenic signaling cascades through autocrine and paracrine mechanisms. Tyrosine kinase receptor (RTK) proteomic arrays, identified PDGF receptor-alpha (PDGFRA) as the predominantly-activated RTK in KSHV-induced mouse KS-tumors. We show that: 1) KSHV lytic replication and the vGPCR can activate PDGFRA through upregulation of its ligands PDGFA/B, which increase c-myc, VEGF and KSHV gene expression in infected cells 2) KSHV infected spindle cells of most AIDS-KS lesions display robust phospho-PDGFRA staining 3) blocking PDGFRA-signaling with N-acetyl-cysteine, RTK-inhibitors Imatinib and Sunitinib, or dominant-negative PDGFRA inhibits tumorigenesis 4) PDGFRA D842V activating-mutation confers resistance to Imatinib in mouse-KS tumorigenesis. Our data show that KSHV usurps sarcomagenic PDGFRA signaling to drive KS. This and the fact that PDGFRA drives non-viral sarcomas highlights the importance for KSHV-induced ligand-mediated activation of PDGFRA in KS sarcomagenesis and shows that this oncogenic axis could be successfully blocked to impede KS tumor growth.
publishDate 2018
dc.date.none.fl_str_mv 2018-07
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/11336/87756
Cavallin, Lucas E.; Ma, Qi; Naipauer, Julian; Gupta, Sachin; Kurian, Mani; et al.; KSHV-induced ligand mediated activation of PDGF receptor-alpha drives Kaposi's sarcomagenesis; Public Library of Science; Plos Pathogens; 14; 7; 7-2018; 1-28
1553-7366
CONICET Digital
CONICET
url http://hdl.handle.net/11336/87756
identifier_str_mv Cavallin, Lucas E.; Ma, Qi; Naipauer, Julian; Gupta, Sachin; Kurian, Mani; et al.; KSHV-induced ligand mediated activation of PDGF receptor-alpha drives Kaposi's sarcomagenesis; Public Library of Science; Plos Pathogens; 14; 7; 7-2018; 1-28
1553-7366
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.ppat.1007175
info:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007175
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 Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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
_version_ 1842268961656274944
score 13.13397

Publicaciones similares