Protein Kinase C Epsilon Cooperates with PTEN Loss for Prostate Tumorigenesis through the CXCL13-CXCR5 Pathway

Autores
Garg, Rachana; Blando, Jorge M.; Perez, Carlos J.; Abba, Martín Carlos; Benavides Agredo, Fernando Andres; Kazanietz, Marcelo Gabriel
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
PKCε, an oncogenic member of the PKC family, is aberrantly overexpressed in epithelial cancers. To date, little is known about functional interactions of PKCε with other genetic alterations, as well as the effectors contributing to its tumorigenic and metastatic phenotype. Here, we demonstrate that PKCε cooperates with the loss of the tumor suppressor Pten for the development of prostate cancer in a mouse model. Mechanistic analysis revealed that PKCε overexpression and Pten loss individually and synergistically upregulate the production of the chemokine CXCL13, which involves the transcriptional activation of the CXCL13 gene via the non-canonical nuclear factor κB (NF-κB) pathway. Notably, targeted disruption of CXCL13 or its receptor, CXCR5, in prostate cancer cells impaired their migratory and tumorigenic properties. In addition to providing evidence for an autonomous vicious cycle driven by PKCε, our studies identified a compelling rationale for targeting the CXCL13-CXCR5 axis for prostate cancer treatment.
Fil: Garg, Rachana. University of Pennsylvania; Estados Unidos
Fil: Blando, Jorge M.. University of Texas; Estados Unidos
Fil: Perez, Carlos J.. University of Texas; Estados Unidos
Fil: Abba, Martín Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina
Fil: Benavides Agredo, Fernando Andres. University of Texas; Estados Unidos
Fil: Kazanietz, Marcelo Gabriel. University of Pennsylvania; Estados Unidos
Materia
Cxcl13
Cxcr5
Migration
Nf-ΚB
PkcΕ
Proliferation
Prostate Cancer
Pten
Transgenic Mice
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/49625
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/49625
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Protein Kinase C Epsilon Cooperates with PTEN Loss for Prostate Tumorigenesis through the CXCL13-CXCR5 PathwayGarg, RachanaBlando, Jorge M.Perez, Carlos J.Abba, Martín CarlosBenavides Agredo, Fernando AndresKazanietz, Marcelo GabrielCxcl13Cxcr5MigrationNf-ΚBPkcΕProliferationProstate CancerPtenTransgenic Micehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1PKCε, an oncogenic member of the PKC family, is aberrantly overexpressed in epithelial cancers. To date, little is known about functional interactions of PKCε with other genetic alterations, as well as the effectors contributing to its tumorigenic and metastatic phenotype. Here, we demonstrate that PKCε cooperates with the loss of the tumor suppressor Pten for the development of prostate cancer in a mouse model. Mechanistic analysis revealed that PKCε overexpression and Pten loss individually and synergistically upregulate the production of the chemokine CXCL13, which involves the transcriptional activation of the CXCL13 gene via the non-canonical nuclear factor κB (NF-κB) pathway. Notably, targeted disruption of CXCL13 or its receptor, CXCR5, in prostate cancer cells impaired their migratory and tumorigenic properties. In addition to providing evidence for an autonomous vicious cycle driven by PKCε, our studies identified a compelling rationale for targeting the CXCL13-CXCR5 axis for prostate cancer treatment.Fil: Garg, Rachana. University of Pennsylvania; Estados UnidosFil: Blando, Jorge M.. University of Texas; Estados UnidosFil: Perez, Carlos J.. University of Texas; Estados UnidosFil: Abba, Martín Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; ArgentinaFil: Benavides Agredo, Fernando Andres. University of Texas; Estados UnidosFil: Kazanietz, Marcelo Gabriel. University of Pennsylvania; Estados UnidosElsevier Science2017-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/49625Garg, Rachana; Blando, Jorge M.; Perez, Carlos J.; Abba, Martín Carlos; Benavides Agredo, Fernando Andres; et al.; Protein Kinase C Epsilon Cooperates with PTEN Loss for Prostate Tumorigenesis through the CXCL13-CXCR5 Pathway; Elsevier Science; Cell Reports; 19; 2; 4-2017; 375-3882211-1247CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2017.03.042info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2211124717303881info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5444089/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:22:01Zoai:ri.conicet.gov.ar:11336/49625instacron: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:34982025-10-15 15:22:01.802CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Protein Kinase C Epsilon Cooperates with PTEN Loss for Prostate Tumorigenesis through the CXCL13-CXCR5 Pathway
title Protein Kinase C Epsilon Cooperates with PTEN Loss for Prostate Tumorigenesis through the CXCL13-CXCR5 Pathway
spellingShingle Protein Kinase C Epsilon Cooperates with PTEN Loss for Prostate Tumorigenesis through the CXCL13-CXCR5 Pathway
Garg, Rachana
Cxcl13
Cxcr5
Migration
Nf-ΚB
PkcΕ
Proliferation
Prostate Cancer
Pten
Transgenic Mice
title_short Protein Kinase C Epsilon Cooperates with PTEN Loss for Prostate Tumorigenesis through the CXCL13-CXCR5 Pathway
title_full Protein Kinase C Epsilon Cooperates with PTEN Loss for Prostate Tumorigenesis through the CXCL13-CXCR5 Pathway
title_fullStr Protein Kinase C Epsilon Cooperates with PTEN Loss for Prostate Tumorigenesis through the CXCL13-CXCR5 Pathway
title_full_unstemmed Protein Kinase C Epsilon Cooperates with PTEN Loss for Prostate Tumorigenesis through the CXCL13-CXCR5 Pathway
title_sort Protein Kinase C Epsilon Cooperates with PTEN Loss for Prostate Tumorigenesis through the CXCL13-CXCR5 Pathway
dc.creator.none.fl_str_mv Garg, Rachana
Blando, Jorge M.
Perez, Carlos J.
Abba, Martín Carlos
Benavides Agredo, Fernando Andres
Kazanietz, Marcelo Gabriel
author Garg, Rachana
author_facet Garg, Rachana
Blando, Jorge M.
Perez, Carlos J.
Abba, Martín Carlos
Benavides Agredo, Fernando Andres
Kazanietz, Marcelo Gabriel
author_role author
author2 Blando, Jorge M.
Perez, Carlos J.
Abba, Martín Carlos
Benavides Agredo, Fernando Andres
Kazanietz, Marcelo Gabriel
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Cxcl13
Cxcr5
Migration
Nf-ΚB
PkcΕ
Proliferation
Prostate Cancer
Pten
Transgenic Mice
topic Cxcl13
Cxcr5
Migration
Nf-ΚB
PkcΕ
Proliferation
Prostate Cancer
Pten
Transgenic Mice
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv PKCε, an oncogenic member of the PKC family, is aberrantly overexpressed in epithelial cancers. To date, little is known about functional interactions of PKCε with other genetic alterations, as well as the effectors contributing to its tumorigenic and metastatic phenotype. Here, we demonstrate that PKCε cooperates with the loss of the tumor suppressor Pten for the development of prostate cancer in a mouse model. Mechanistic analysis revealed that PKCε overexpression and Pten loss individually and synergistically upregulate the production of the chemokine CXCL13, which involves the transcriptional activation of the CXCL13 gene via the non-canonical nuclear factor κB (NF-κB) pathway. Notably, targeted disruption of CXCL13 or its receptor, CXCR5, in prostate cancer cells impaired their migratory and tumorigenic properties. In addition to providing evidence for an autonomous vicious cycle driven by PKCε, our studies identified a compelling rationale for targeting the CXCL13-CXCR5 axis for prostate cancer treatment.
Fil: Garg, Rachana. University of Pennsylvania; Estados Unidos
Fil: Blando, Jorge M.. University of Texas; Estados Unidos
Fil: Perez, Carlos J.. University of Texas; Estados Unidos
Fil: Abba, Martín Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina
Fil: Benavides Agredo, Fernando Andres. University of Texas; Estados Unidos
Fil: Kazanietz, Marcelo Gabriel. University of Pennsylvania; Estados Unidos
description PKCε, an oncogenic member of the PKC family, is aberrantly overexpressed in epithelial cancers. To date, little is known about functional interactions of PKCε with other genetic alterations, as well as the effectors contributing to its tumorigenic and metastatic phenotype. Here, we demonstrate that PKCε cooperates with the loss of the tumor suppressor Pten for the development of prostate cancer in a mouse model. Mechanistic analysis revealed that PKCε overexpression and Pten loss individually and synergistically upregulate the production of the chemokine CXCL13, which involves the transcriptional activation of the CXCL13 gene via the non-canonical nuclear factor κB (NF-κB) pathway. Notably, targeted disruption of CXCL13 or its receptor, CXCR5, in prostate cancer cells impaired their migratory and tumorigenic properties. In addition to providing evidence for an autonomous vicious cycle driven by PKCε, our studies identified a compelling rationale for targeting the CXCL13-CXCR5 axis for prostate cancer treatment.
publishDate 2017
dc.date.none.fl_str_mv 2017-04
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/11336/49625
Garg, Rachana; Blando, Jorge M.; Perez, Carlos J.; Abba, Martín Carlos; Benavides Agredo, Fernando Andres; et al.; Protein Kinase C Epsilon Cooperates with PTEN Loss for Prostate Tumorigenesis through the CXCL13-CXCR5 Pathway; Elsevier Science; Cell Reports; 19; 2; 4-2017; 375-388
2211-1247
CONICET Digital
CONICET
url http://hdl.handle.net/11336/49625
identifier_str_mv Garg, Rachana; Blando, Jorge M.; Perez, Carlos J.; Abba, Martín Carlos; Benavides Agredo, Fernando Andres; et al.; Protein Kinase C Epsilon Cooperates with PTEN Loss for Prostate Tumorigenesis through the CXCL13-CXCR5 Pathway; Elsevier Science; Cell Reports; 19; 2; 4-2017; 375-388
2211-1247
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2017.03.042
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2211124717303881
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5444089/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier 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_ 1846083367500513280
score 13.22299

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