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

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...

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Detalles Bibliográficos
Autores principales:	Garg, R., Blando, Jorge M., Pérez, Carlos J., Abba, Martín Carlos, Benavides, Fernando, Kazanietz, Marcelo
Formato:	Articulo
Lenguaje:	Inglés
Publicado:	2017
Materias:	Ciencias Médicas CXCL13 CXCR5 migration NF-κB PKCε proliferation prostate cancer PTEN transgenic mice
Acceso en línea:	http://sedici.unlp.edu.ar/handle/10915/87748
Aporte de:	SEDICI (UNLP) de Universidad Nacional de La Plata

id	I19-R120-10915-87748
record_format	dspace
institution	Universidad Nacional de La Plata
institution_str	I-19
repository_str	R-120
collection	SEDICI (UNLP)
language	Inglés
topic	Ciencias Médicas CXCL13 CXCR5 migration NF-κB PKCε proliferation prostate cancer PTEN transgenic mice
spellingShingle	Ciencias Médicas CXCL13 CXCR5 migration NF-κB PKCε proliferation prostate cancer PTEN transgenic mice Garg, R. Blando, Jorge M. Pérez, Carlos J. Abba, Martín Carlos Benavides, Fernando Kazanietz, Marcelo Protein Kinase C Epsilon Cooperates with PTEN Loss for Prostate Tumorigenesis through the CXCL13-CXCR5 Pathway
topic_facet	Ciencias Médicas CXCL13 CXCR5 migration NF-κB PKCε proliferation prostate cancer PTEN transgenic mice
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.
format	Articulo Articulo
author	Garg, R. Blando, Jorge M. Pérez, Carlos J. Abba, Martín Carlos Benavides, Fernando Kazanietz, Marcelo
author_facet	Garg, R. Blando, Jorge M. Pérez, Carlos J. Abba, Martín Carlos Benavides, Fernando Kazanietz, Marcelo
author_sort	Garg, R.
title	Protein Kinase C Epsilon Cooperates with PTEN Loss for Prostate Tumorigenesis through the CXCL13-CXCR5 Pathway
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
publishDate	2017
url	http://sedici.unlp.edu.ar/handle/10915/87748
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Protein Kinase C Epsilon Cooperates with PTEN Loss for Prostate Tumorigenesis through the CXCL13-CXCR5 Pathway

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