Spatial and temporal proteome dynamics of glioma cells during oncolytic adenovirus Delta-24-RGD infection

González Morales, Andrea; Zabaleta, Aintzane; Guruceaga, Elizabeth; Alonso Roldán, Marta; García Moure, Marc

Publication:
Spatial and temporal proteome dynamics of glioma cells during oncolytic adenovirus Delta-24-RGD infection

dc.contributor.author	González Morales, Andrea
dc.contributor.author	Zabaleta, Aintzane
dc.contributor.author	Guruceaga, Elizabeth
dc.contributor.author	Alonso Roldán, Marta
dc.contributor.author	García Moure, Marc
dc.contributor.department	Ciencias de la Salud	es_ES
dc.contributor.department	Osasun Zientziak	eu
dc.contributor.funder	Gobierno de Navarra / Nafarroako Gobernua	es
dc.date.accessioned	2020-11-18T09:18:31Z
dc.date.available	2020-11-18T09:18:31Z
dc.date.issued	2018
dc.description.abstract	Glioblastoma multiforme (GBM) is the most common and aggressive type of malignant glioma. Oncolytic adenoviruses are being modified to exploit the aberrant expression of proteins in tumor cells to increase the antiglioma efficacy. E1A mutant adenovirus Delta-24-RGD (DNX-2401) has shown a favorable toxicity profile and remarkable efficacy in a first-in-human phase I clinical trial. However, the comprehensive modulation of glioma metabolism in response to Delta-24-RGD infection is poorly understood. Integrating mass spectrometry based-quantitative proteomics, physical and functional interaction data, and biochemical approaches, we conducted a cell-wide study of cytosolic, nuclear, and secreted glioma proteomes throughout the early time course of Delta-24-RGD infection. In addition to the severe proteostasis impairment detected during the first hours post-infection (hpi), Delta-24-RGD induces a transient inhibition of signal transducer and activator of transcription 3 (STAT3), and transcription factor AP-1 (c-JUN) between 3 and 10hpi, increasing the nuclear factor kappa B (NF-κB) activity at 6hpi. Furthermore, Delta-24-RGD specifically modulates the activation dynamics of protein kinase C (PKC), extracellular signal–regulated kinase 1/2 (ERK1/2), and p38 mitogen-activated protein kinase (p38 MAPK) pathways early in infection. At extracellular level, Delta-24-RGD triggers a time –dependent dynamic production of multitasking cytokines, and chemotactic factors, suggesting potential pleiotropic effects on the immune system reactivation. Taken together, these data help us to understand the mechanisms used by Delta-24-RGD to exploit glioma proteome organization. Further mining of this proteomic resource may enable design and engineering complementary adenoviral based-vectors to increase the specificity and potency against glioma.	en
dc.description.sponsorship	This work was funded by grants from the Spanish Ministry of Economy and Competitiveness (MINECO) (Ref. SAF2014-59340-R To ES), the Department of Economic Development from Government of Navarra (ref. PC025, PC023-24, PC81-82, PI059 to ES and PI031 to JFI), the Instituto de Salud Carlos III and Fondos Feder Europeos (PI16/00066 to MMA), the Spanish Ministry of Science and Innovation (IEDI2015-00638 to MMA), the Department of Health of the Government of Navarra (to MMA), the Basque Foundation for Health Research (BIOEF, BIO13/CI/005 to MMA), Asociación Pablo Ugarte-Fuerza, Julen (to MMA). AGM was supported by PEJ-2014-A-61949 (MINECO).	en
dc.format.extent	21 p.
dc.format.mimetype	application/pdf	en
dc.format.mimetype	application/zip	en
dc.identifier.doi	10.18632/oncotarget.25774
dc.identifier.issn	1949-2553
dc.identifier.uri	https://academica-e.unavarra.es/handle/2454/38719
dc.language.iso	eng	en
dc.publisher	Impact Journals	en
dc.relation.ispartof	Oncotarget, 2018, 9, 31045-31065	en
dc.relation.projectID	info:eu-repo/grantAgreement/MINECO//SAF2014-59340-R/ES/	en
dc.relation.publisherversion	https://doi.org/10.18632/oncotarget.25774
dc.rights	Creative Commons Attribution 3.0 Unported (CC BY 3.0)	en
dc.rights.accessRights	info:eu-repo/semantics/openAccess	en
dc.rights.accessRights	Acceso abierto / Sarbide irekia	es
dc.rights.uri	http://creativecommons.org/licenses/by/3.0/
dc.subject	Adenovirus	en
dc.subject	Delta-24RGD infection	en
dc.subject	Proteomics	en
dc.subject	Glioma	en
dc.title	Spatial and temporal proteome dynamics of glioma cells during oncolytic adenovirus Delta-24-RGD infection	en
dc.type	info:eu-repo/semantics/article	en
dc.type	Artículo / Artikulua	es
dc.type.version	info:eu-repo/semantics/publishedVersion	en
dc.type.version	Versión publicada / Argitaratu den bertsioa	es
dspace.entity.type	Publication
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