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dc.contributor.author
Wu, Yonghe
dc.contributor.author
Tedesco, Lucas
dc.contributor.author
Kristin, Lucia
dc.contributor.author
Schlitter, Anna M.
dc.contributor.author
Monteserin Garcia, Jose
dc.contributor.author
Esposito, Irene
dc.contributor.author
Auernhammer, Christoph J.
dc.contributor.author
Theodoropoulou, Marily
dc.contributor.author
Arzt, Eduardo Simon
dc.contributor.author
Renner, Ulrich
dc.contributor.author
Stalla, Günter K.
dc.date.available
2018-06-26T23:13:31Z
dc.date.issued
2016-09
dc.identifier.citation
Wu, Yonghe; Tedesco, Lucas; Kristin, Lucia; Schlitter, Anna M.; Monteserin Garcia, Jose; et al.; RSUME is implicated in tumorigenesis and metastasis of pancreatic neuroendocrine tumors; Impact Journals LLC; Oncotarget; 7; 36; 9-2016; 57878-57893
dc.identifier.issn
1949-2553
dc.identifier.uri
http://hdl.handle.net/11336/50217
dc.description.abstract
The factors triggering pancreatic neuroendocrine tumor (PanNET) progression are largely unknown. Here we investigated the role and mechanisms of the sumoylation enhancing protein RSUME in PanNET tumorigenesis. Immunohistochemical studies showed that RSUME is strongly expressed in normal human pancreas, in particular in β-cells. RSUME expression is reduced in insulinomas and is nearly absent in other types of PanNETs suggesting a role in PanNET tumorigenesis. In human pancreatic neuroendocrine BON1 cells, RSUME stimulates hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor-A (VEGF-A), which are key components of tumor neovascularisation. In contrast, RSUME suppresses nuclear factor-κB (NF-κB) and its target interleukin-8 (IL-8). Correspondingly, PanNET cells with RSUME knockdown showed decreased HIF-1α activity and increased NF-κB and IL-8 production leading to a moderate reduction of VEGF-A release as reduced HIF-1α/VEGF-A production is partly compensated by NF-κB/IL-8-induced VEGF-A. Notably, RSUME stabilizes the tumor suppressor PTEN, which is frequently lost in PanNETs and whose absence is associated with metastasis formation. In vivo orthotopic transplantation of PanNET cells with or without RSUME expression into nude mice showed that PanNETs without RSUME have reduced PTEN expression, grow faster and form multiple liver metastases. In sum, RSUME differentially regulates key components of PanNET formation suggesting that the observed loss of RSUME in advanced PanNETs is critically involved in PanNET tumorigenesis, particularly in metastasis formation.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Impact Journals LLC
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Angiogenesis
dc.subject
Metastasis
dc.subject
Pannets
dc.subject
Rsume
dc.subject
Rwdd3
dc.subject.classification
Inmunología
dc.subject.classification
Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
RSUME is implicated in tumorigenesis and metastasis of pancreatic neuroendocrine tumors
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-06-22T14:35:32Z
dc.journal.volume
7
dc.journal.number
36
dc.journal.pagination
57878-57893
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Wu, Yonghe. Max Planck Institute of Psychiatry; Alemania
dc.description.fil
Fil: Tedesco, Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
dc.description.fil
Fil: Kristin, Lucia. Max Planck Institute of Psychiatry; Alemania
dc.description.fil
Fil: Schlitter, Anna M.. Universitat Technical Zu Munich; Alemania
dc.description.fil
Fil: Monteserin Garcia, Jose. Max Planck Institute of Psychiatry; Alemania
dc.description.fil
Fil: Esposito, Irene. Universitat Technical Zu Munich; Alemania
dc.description.fil
Fil: Auernhammer, Christoph J.. Universitat Technical Zu Munich; Alemania
dc.description.fil
Fil: Theodoropoulou, Marily. Max Planck Institute of Psychiatry; Alemania
dc.description.fil
Fil: Arzt, Eduardo Simon. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
dc.description.fil
Fil: Renner, Ulrich. Max Planck Institute of Psychiatry; Alemania
dc.description.fil
Fil: Stalla, Günter K.. Max Planck Institute of Psychiatry; Alemania
dc.journal.title
Oncotarget
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.18632/oncotarget.11081
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=11081&path[]=35094


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