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dc.contributor.author
Gilabert, Mariana
dc.contributor.author
Vaccaro, Maria Ines
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Fernandez Zapico, Martín E.
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Calvo, Ezequiel L.
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Turrini, Olivier
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Secq, Véronique
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Garcia, Stéphanie
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Moutardier, Vincent
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Lomberk, Gwen
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Dusetti, Nelson
dc.contributor.author
Urrutia, Raul
dc.contributor.author
Iovanna, Juan L.
dc.date.available
2017-01-17T15:10:31Z
dc.date.issued
2013-09
dc.identifier.citation
Gilabert, Mariana; Vaccaro, Maria Ines; Fernandez Zapico, Martín E.; Calvo, Ezequiel L.; Turrini, Olivier; et al.; Novel role of VMP1 as modifier of the pancreatic tumor cell response to chemotherapeutic drugs; Wiley; Journal of Cell Physiology; 228; 9; 9-2013; 1834-1843
dc.identifier.issn
1097-4652
dc.identifier.uri
http://hdl.handle.net/11336/11462
dc.description.abstract
We hypothesized that inhibiting molecules that mediate the adaptation response to cellular stress can antagonize the resistance of pancreatic cancer cells to chemotherapeutic drugs. Toward this end, here, we investigated how VMP1, a stress-induced autophagy-associated protein, modulate stress responses triggered by chemotherapeutic agents in PDAC. We find that VMP1 is particularly over-expressed in poorly differentiated human pancreatic cancer. Pharmacological studies show that drugs that work, in part, via the endoplasmic reticulum stress response, induce VMP1 expression. Similarly, VMP1 is induced by known endoplasmic reticulum stress activators. Genetic inactivation of VMP1 using RNAi-based antagonize the pancreatic cancer stress response to antitumoral agents. Functionally, we find that VMP1 regulates both autophagy and chemotherapeutic resistance even in the presence of chloroquin, ATG5 or Beclin 1 siRNAs, or a Beclin 1-binding VMP1 mutant. In addition, VMP1 modulates endoplasmic reticulum stress independently of its coupling to the molecular and cellular autophagy machinery. Preclinical studies demonstrate that xenografts expressing an inducible and tractable form of VMP1 show increased resistance to the gemcitabine treatment. These results underscore a novel role for VMP1 as a potential therapeutic target for combinatorial therapies aimed at sensitizing pancreatic cancer cells to chemotherapeutic agents as well as provide novel molecular mechanisms to better understand this phenomenon.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Wiley
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Vmp1
dc.subject
Pancreatic Cancer
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Autophagy
dc.subject.classification
Bioquímica y Biología Molecular
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Novel role of VMP1 as modifier of the pancreatic tumor cell response to chemotherapeutic drugs
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-11-24T17:20:33Z
dc.journal.volume
228
dc.journal.number
9
dc.journal.pagination
1834-1843
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Hoboken
dc.description.fil
Fil: Gilabert, Mariana. Cancer Research Center of Marseille; Francia. Aix-Marseille University; Francia. Centre National de la Recherche Scientifique; Francia
dc.description.fil
Fil: Vaccaro, Maria Ines. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular; Argentina
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Fil: Fernandez Zapico, Martín E.. Mayo Clinic Cancer Center; Estados Unidos
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Fil: Calvo, Ezequiel L.. Molecular Endocrinology and Oncology Research Center; Canadá
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Fil: Turrini, Olivier. Cancer Research Center of Marseille; Francia. Aix-Marseille University; Francia. Centre National de la Recherche Scientifique; Francia
dc.description.fil
Fil: Secq, Véronique. Cancer Research Center of Marseille; Francia. Aix-Marseille University; Francia. Centre National de la Recherche Scientifique; Francia
dc.description.fil
Fil: Garcia, Stéphanie. Cancer Research Center of Marseille; Francia. Aix-Marseille University; Francia. Centre National de la Recherche Scientifique; Francia
dc.description.fil
Fil: Moutardier, Vincent. Cancer Research Center of Marseille; Francia. Aix-Marseille University; Francia. Centre National de la Recherche Scientifique; Francia
dc.description.fil
Fil: Lomberk, Gwen. Mayo Clinic; Estados Unidos
dc.description.fil
Fil: Dusetti, Nelson. Cancer Research Center of Marseille; Francia. Aix-Marseille University; Francia. Centre National de la Recherche Scientifique; Francia
dc.description.fil
Fil: Urrutia, Raul. Mayo Clinic; Estados Unidos
dc.description.fil
Fil: Iovanna, Juan L.. Cancer Research Center of Marseille; Francia. Aix-Marseille University; Francia. Centre National de la Recherche Scientifique; Francia
dc.journal.title
Journal of Cell Physiology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4048029/
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://onlinelibrary.wiley.com/doi/10.1002/jcp.24343/full
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1002/jcp.24343
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