RSUME is implicated in tumorigenesis and metastasis of pancreatic neuroendocrine tumors

Autores
Wu, Yonghe; Tedesco, Lucas; Kristin, Lucia; Schlitter, Anna M.; Monteserin Garcia, Jose; Esposito, Irene; Auernhammer, Christoph J.; Theodoropoulou, Marily; Arzt, Eduardo Simon; Renner, Ulrich; Stalla, Günter K.
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Wu, Yonghe. Max Planck Institute of Psychiatry; Alemania
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
Fil: Kristin, Lucia. Max Planck Institute of Psychiatry; Alemania
Fil: Schlitter, Anna M.. Universitat Technical Zu Munich; Alemania
Fil: Monteserin Garcia, Jose. Max Planck Institute of Psychiatry; Alemania
Fil: Esposito, Irene. Universitat Technical Zu Munich; Alemania
Fil: Auernhammer, Christoph J.. Universitat Technical Zu Munich; Alemania
Fil: Theodoropoulou, Marily. Max Planck Institute of Psychiatry; Alemania
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
Fil: Renner, Ulrich. Max Planck Institute of Psychiatry; Alemania
Fil: Stalla, Günter K.. Max Planck Institute of Psychiatry; Alemania
Materia
ANGIOGENESIS
METASTASIS
PANNETS
RSUME
RWDD3
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/50217
Acceder
id CONICETDig_a6a38bbc1b799d230dea73d8d8b0bc73
oai_identifier_str oai:ri.conicet.gov.ar:11336/50217
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling RSUME is implicated in tumorigenesis and metastasis of pancreatic neuroendocrine tumorsWu, YongheTedesco, LucasKristin, LuciaSchlitter, Anna M.Monteserin Garcia, JoseEsposito, IreneAuernhammer, Christoph J.Theodoropoulou, MarilyArzt, Eduardo SimonRenner, UlrichStalla, Günter K.ANGIOGENESISMETASTASISPANNETSRSUMERWDD3https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The 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.Fil: Wu, Yonghe. Max Planck Institute of Psychiatry; AlemaniaFil: 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; ArgentinaFil: Kristin, Lucia. Max Planck Institute of Psychiatry; AlemaniaFil: Schlitter, Anna M.. Universitat Technical Zu Munich; AlemaniaFil: Monteserin Garcia, Jose. Max Planck Institute of Psychiatry; AlemaniaFil: Esposito, Irene. Universitat Technical Zu Munich; AlemaniaFil: Auernhammer, Christoph J.. Universitat Technical Zu Munich; AlemaniaFil: Theodoropoulou, Marily. Max Planck Institute of Psychiatry; AlemaniaFil: 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; ArgentinaFil: Renner, Ulrich. Max Planck Institute of Psychiatry; AlemaniaFil: Stalla, Günter K.. Max Planck Institute of Psychiatry; AlemaniaImpact Journals LLC2016-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/50217Wu, 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; 57878-578931949-2553CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.11081info:eu-repo/semantics/altIdentifier/url/http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=11081&path[]=35094info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:49:59Zoai:ri.conicet.gov.ar:11336/50217instacron: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:34982025-09-03 09:50:00.125CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv RSUME is implicated in tumorigenesis and metastasis of pancreatic neuroendocrine tumors
title RSUME is implicated in tumorigenesis and metastasis of pancreatic neuroendocrine tumors
spellingShingle RSUME is implicated in tumorigenesis and metastasis of pancreatic neuroendocrine tumors
Wu, Yonghe
ANGIOGENESIS
METASTASIS
PANNETS
RSUME
RWDD3
title_short RSUME is implicated in tumorigenesis and metastasis of pancreatic neuroendocrine tumors
title_full RSUME is implicated in tumorigenesis and metastasis of pancreatic neuroendocrine tumors
title_fullStr RSUME is implicated in tumorigenesis and metastasis of pancreatic neuroendocrine tumors
title_full_unstemmed RSUME is implicated in tumorigenesis and metastasis of pancreatic neuroendocrine tumors
title_sort RSUME is implicated in tumorigenesis and metastasis of pancreatic neuroendocrine tumors
dc.creator.none.fl_str_mv Wu, Yonghe
Tedesco, Lucas
Kristin, Lucia
Schlitter, Anna M.
Monteserin Garcia, Jose
Esposito, Irene
Auernhammer, Christoph J.
Theodoropoulou, Marily
Arzt, Eduardo Simon
Renner, Ulrich
Stalla, Günter K.
author Wu, Yonghe
author_facet Wu, Yonghe
Tedesco, Lucas
Kristin, Lucia
Schlitter, Anna M.
Monteserin Garcia, Jose
Esposito, Irene
Auernhammer, Christoph J.
Theodoropoulou, Marily
Arzt, Eduardo Simon
Renner, Ulrich
Stalla, Günter K.
author_role author
author2 Tedesco, Lucas
Kristin, Lucia
Schlitter, Anna M.
Monteserin Garcia, Jose
Esposito, Irene
Auernhammer, Christoph J.
Theodoropoulou, Marily
Arzt, Eduardo Simon
Renner, Ulrich
Stalla, Günter K.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ANGIOGENESIS
METASTASIS
PANNETS
RSUME
RWDD3
topic ANGIOGENESIS
METASTASIS
PANNETS
RSUME
RWDD3
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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.
Fil: Wu, Yonghe. Max Planck Institute of Psychiatry; Alemania
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
Fil: Kristin, Lucia. Max Planck Institute of Psychiatry; Alemania
Fil: Schlitter, Anna M.. Universitat Technical Zu Munich; Alemania
Fil: Monteserin Garcia, Jose. Max Planck Institute of Psychiatry; Alemania
Fil: Esposito, Irene. Universitat Technical Zu Munich; Alemania
Fil: Auernhammer, Christoph J.. Universitat Technical Zu Munich; Alemania
Fil: Theodoropoulou, Marily. Max Planck Institute of Psychiatry; Alemania
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
Fil: Renner, Ulrich. Max Planck Institute of Psychiatry; Alemania
Fil: Stalla, Günter K.. Max Planck Institute of Psychiatry; Alemania
description 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.
publishDate 2016
dc.date.none.fl_str_mv 2016-09
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/11336/50217
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
1949-2553
CONICET Digital
CONICET
url http://hdl.handle.net/11336/50217
identifier_str_mv 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
1949-2553
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.11081
info:eu-repo/semantics/altIdentifier/url/http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=11081&path[]=35094
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Impact Journals LLC
publisher.none.fl_str_mv Impact Journals LLC
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_ 1842269006250115072
score 13.13397

Publicaciones similares