Nuclear protein 1 promotes pancreatic cancer development and protects cells from stress by inhibiting apoptosis

Autores
Hamidi, Tewfik; Algül, Hana; Cano, Carla Eliana; Sandi, Maria José; Molejon, Maria Ines; Riemann, Marc; Calvo, Ezequiel Luis; Lomberk, Gwen; Dagorn, Jean Charles; Weih, Falk; Urrutia, Raul; Schmid, Roland Michael; Iovanna, Juan Lucio
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Pancreatic ductal adenocarcinoma (PDAC) has the lowest survival rate of all cancers and shows remarkable resistance to cell stress. Nuclear protein 1 (Nupr1), which mediates stress response in the pancreas, is frequently upregulated in pancreatic cancer. Here, we report that Nupr1 plays an essential role in pancreatic tumorigenesis. In a mouse model of pancreatic cancer with constitutively expressed oncogenic KrasG12D, we found that loss of Nupr1 protected from the development of pancreatic intraepithelial neoplasias (PanINs). Further, in cultured pancreatic cells, nutrient deprivation activated Nupr1 expression, which we found to be required for cell survival. We found that Nupr1 protected cells from stress-induced death by inhibiting apoptosis through a pathway dependent on transcription factor RelB and immediate early response 3 (IER3). NUPR1, RELB, and IER3 proteins were coexpressed in mouse PanINs from KrasG12D-expressing pancreas. Moreover, pancreasspecific deletion of Relb in a KrasG12D background resulted in delayed in PanIN development associated with a lack of IER3 expression. Thus, efficient PanIN formation was dependent on the expression of Nupr1 and Relb, with likely involvement of IER3. Finally, in patients with PDAC, expression of NUPR1, RELB, and IER3 was significantly correlated with a poor prognosis. Cumulatively, these results reveal a NUPR1/RELB/IER3 stress-related pathway that is required for oncogenic KrasG12D-dependent transformation of the pancreas.
Fil: Hamidi, Tewfik. Centre de Recherche En Cancérologie de Marseille; Francia. Inserm; Francia. Aix-Marseille Université; Francia
Fil: Algül, Hana. Technical University of Munich; Alemania
Fil: Cano, Carla Eliana. Centre de Recherche En Cancérologie de Marseille; Francia. Inserm; Francia. Aix-Marseille Université; Francia
Fil: Sandi, Maria José. Centre de Recherche En Cancérologie de Marseille; Francia. Inserm; Francia. Aix-Marseille Université; Francia
Fil: Molejon, Maria Ines. Centre de Recherche En Cancérologie de Marseille; Francia. Inserm; Francia. Aix-Marseille Université; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Riemann, Marc. Leibniz-Institut für Altersforschung; Alemania
Fil: Calvo, Ezequiel Luis. Molecular Endocrinology and Oncology Research Center; Canadá
Fil: Lomberk, Gwen. Laboratory of Epigenetics and Chromatin Dynamics; Estados Unidos
Fil: Dagorn, Jean Charles. Centre de Recherche En Cancérologie de Marseille; Francia. Inserm; Francia. Aix-Marseille Université; Francia
Fil: Weih, Falk. Leibniz-Institut für Altersforschung; Alemania
Fil: Urrutia, Raul. Laboratory of Epigenetics and Chromatin Dynamics; Estados Unidos
Fil: Schmid, Roland Michael. Technical University of Munich; Alemania
Fil: Iovanna, Juan Lucio. Centre de Recherche En Cancérologie de Marseille; Francia. Inserm; Francia. Aix-Marseille Université; Francia
Materia
Nupr1
Pancreatic Cancer
Pancreas
Apoptosis
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:11336/216511
Acceder
id CONICETDig_5dd22663e48b7c86b34fafaaedd68c4a
oai_identifier_str oai:ri.conicet.gov.ar:11336/216511
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Nuclear protein 1 promotes pancreatic cancer development and protects cells from stress by inhibiting apoptosisHamidi, TewfikAlgül, HanaCano, Carla ElianaSandi, Maria JoséMolejon, Maria InesRiemann, MarcCalvo, Ezequiel LuisLomberk, GwenDagorn, Jean CharlesWeih, FalkUrrutia, RaulSchmid, Roland MichaelIovanna, Juan LucioNupr1Pancreatic CancerPancreasApoptosishttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Pancreatic ductal adenocarcinoma (PDAC) has the lowest survival rate of all cancers and shows remarkable resistance to cell stress. Nuclear protein 1 (Nupr1), which mediates stress response in the pancreas, is frequently upregulated in pancreatic cancer. Here, we report that Nupr1 plays an essential role in pancreatic tumorigenesis. In a mouse model of pancreatic cancer with constitutively expressed oncogenic KrasG12D, we found that loss of Nupr1 protected from the development of pancreatic intraepithelial neoplasias (PanINs). Further, in cultured pancreatic cells, nutrient deprivation activated Nupr1 expression, which we found to be required for cell survival. We found that Nupr1 protected cells from stress-induced death by inhibiting apoptosis through a pathway dependent on transcription factor RelB and immediate early response 3 (IER3). NUPR1, RELB, and IER3 proteins were coexpressed in mouse PanINs from KrasG12D-expressing pancreas. Moreover, pancreasspecific deletion of Relb in a KrasG12D background resulted in delayed in PanIN development associated with a lack of IER3 expression. Thus, efficient PanIN formation was dependent on the expression of Nupr1 and Relb, with likely involvement of IER3. Finally, in patients with PDAC, expression of NUPR1, RELB, and IER3 was significantly correlated with a poor prognosis. Cumulatively, these results reveal a NUPR1/RELB/IER3 stress-related pathway that is required for oncogenic KrasG12D-dependent transformation of the pancreas.Fil: Hamidi, Tewfik. Centre de Recherche En Cancérologie de Marseille; Francia. Inserm; Francia. Aix-Marseille Université; FranciaFil: Algül, Hana. Technical University of Munich; AlemaniaFil: Cano, Carla Eliana. Centre de Recherche En Cancérologie de Marseille; Francia. Inserm; Francia. Aix-Marseille Université; FranciaFil: Sandi, Maria José. Centre de Recherche En Cancérologie de Marseille; Francia. Inserm; Francia. Aix-Marseille Université; FranciaFil: Molejon, Maria Ines. Centre de Recherche En Cancérologie de Marseille; Francia. Inserm; Francia. Aix-Marseille Université; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Riemann, Marc. Leibniz-Institut für Altersforschung; AlemaniaFil: Calvo, Ezequiel Luis. Molecular Endocrinology and Oncology Research Center; CanadáFil: Lomberk, Gwen. Laboratory of Epigenetics and Chromatin Dynamics; Estados UnidosFil: Dagorn, Jean Charles. Centre de Recherche En Cancérologie de Marseille; Francia. Inserm; Francia. Aix-Marseille Université; FranciaFil: Weih, Falk. Leibniz-Institut für Altersforschung; AlemaniaFil: Urrutia, Raul. Laboratory of Epigenetics and Chromatin Dynamics; Estados UnidosFil: Schmid, Roland Michael. Technical University of Munich; AlemaniaFil: Iovanna, Juan Lucio. Centre de Recherche En Cancérologie de Marseille; Francia. Inserm; Francia. Aix-Marseille Université; FranciaAmerican Society for Clinical Investigation2012-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/216511Hamidi, Tewfik; Algül, Hana; Cano, Carla Eliana; Sandi, Maria José; Molejon, Maria Ines; et al.; Nuclear protein 1 promotes pancreatic cancer development and protects cells from stress by inhibiting apoptosis; American Society for Clinical Investigation; Journal of Clinical Investigation; 122; 6; 6-2012; 2092-21030021-9738CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1172/jci60144info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366404/info:eu-repo/semantics/altIdentifier/url/https://www.jci.org/articles/view/60144info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:24:35Zoai:ri.conicet.gov.ar:11336/216511instacron: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:34982025-10-15 15:24:36.105CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Nuclear protein 1 promotes pancreatic cancer development and protects cells from stress by inhibiting apoptosis
title Nuclear protein 1 promotes pancreatic cancer development and protects cells from stress by inhibiting apoptosis
spellingShingle Nuclear protein 1 promotes pancreatic cancer development and protects cells from stress by inhibiting apoptosis
Hamidi, Tewfik
Nupr1
Pancreatic Cancer
Pancreas
Apoptosis
title_short Nuclear protein 1 promotes pancreatic cancer development and protects cells from stress by inhibiting apoptosis
title_full Nuclear protein 1 promotes pancreatic cancer development and protects cells from stress by inhibiting apoptosis
title_fullStr Nuclear protein 1 promotes pancreatic cancer development and protects cells from stress by inhibiting apoptosis
title_full_unstemmed Nuclear protein 1 promotes pancreatic cancer development and protects cells from stress by inhibiting apoptosis
title_sort Nuclear protein 1 promotes pancreatic cancer development and protects cells from stress by inhibiting apoptosis
dc.creator.none.fl_str_mv Hamidi, Tewfik
Algül, Hana
Cano, Carla Eliana
Sandi, Maria José
Molejon, Maria Ines
Riemann, Marc
Calvo, Ezequiel Luis
Lomberk, Gwen
Dagorn, Jean Charles
Weih, Falk
Urrutia, Raul
Schmid, Roland Michael
Iovanna, Juan Lucio
author Hamidi, Tewfik
author_facet Hamidi, Tewfik
Algül, Hana
Cano, Carla Eliana
Sandi, Maria José
Molejon, Maria Ines
Riemann, Marc
Calvo, Ezequiel Luis
Lomberk, Gwen
Dagorn, Jean Charles
Weih, Falk
Urrutia, Raul
Schmid, Roland Michael
Iovanna, Juan Lucio
author_role author
author2 Algül, Hana
Cano, Carla Eliana
Sandi, Maria José
Molejon, Maria Ines
Riemann, Marc
Calvo, Ezequiel Luis
Lomberk, Gwen
Dagorn, Jean Charles
Weih, Falk
Urrutia, Raul
Schmid, Roland Michael
Iovanna, Juan Lucio
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Nupr1
Pancreatic Cancer
Pancreas
Apoptosis
topic Nupr1
Pancreatic Cancer
Pancreas
Apoptosis
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Pancreatic ductal adenocarcinoma (PDAC) has the lowest survival rate of all cancers and shows remarkable resistance to cell stress. Nuclear protein 1 (Nupr1), which mediates stress response in the pancreas, is frequently upregulated in pancreatic cancer. Here, we report that Nupr1 plays an essential role in pancreatic tumorigenesis. In a mouse model of pancreatic cancer with constitutively expressed oncogenic KrasG12D, we found that loss of Nupr1 protected from the development of pancreatic intraepithelial neoplasias (PanINs). Further, in cultured pancreatic cells, nutrient deprivation activated Nupr1 expression, which we found to be required for cell survival. We found that Nupr1 protected cells from stress-induced death by inhibiting apoptosis through a pathway dependent on transcription factor RelB and immediate early response 3 (IER3). NUPR1, RELB, and IER3 proteins were coexpressed in mouse PanINs from KrasG12D-expressing pancreas. Moreover, pancreasspecific deletion of Relb in a KrasG12D background resulted in delayed in PanIN development associated with a lack of IER3 expression. Thus, efficient PanIN formation was dependent on the expression of Nupr1 and Relb, with likely involvement of IER3. Finally, in patients with PDAC, expression of NUPR1, RELB, and IER3 was significantly correlated with a poor prognosis. Cumulatively, these results reveal a NUPR1/RELB/IER3 stress-related pathway that is required for oncogenic KrasG12D-dependent transformation of the pancreas.
Fil: Hamidi, Tewfik. Centre de Recherche En Cancérologie de Marseille; Francia. Inserm; Francia. Aix-Marseille Université; Francia
Fil: Algül, Hana. Technical University of Munich; Alemania
Fil: Cano, Carla Eliana. Centre de Recherche En Cancérologie de Marseille; Francia. Inserm; Francia. Aix-Marseille Université; Francia
Fil: Sandi, Maria José. Centre de Recherche En Cancérologie de Marseille; Francia. Inserm; Francia. Aix-Marseille Université; Francia
Fil: Molejon, Maria Ines. Centre de Recherche En Cancérologie de Marseille; Francia. Inserm; Francia. Aix-Marseille Université; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Riemann, Marc. Leibniz-Institut für Altersforschung; Alemania
Fil: Calvo, Ezequiel Luis. Molecular Endocrinology and Oncology Research Center; Canadá
Fil: Lomberk, Gwen. Laboratory of Epigenetics and Chromatin Dynamics; Estados Unidos
Fil: Dagorn, Jean Charles. Centre de Recherche En Cancérologie de Marseille; Francia. Inserm; Francia. Aix-Marseille Université; Francia
Fil: Weih, Falk. Leibniz-Institut für Altersforschung; Alemania
Fil: Urrutia, Raul. Laboratory of Epigenetics and Chromatin Dynamics; Estados Unidos
Fil: Schmid, Roland Michael. Technical University of Munich; Alemania
Fil: Iovanna, Juan Lucio. Centre de Recherche En Cancérologie de Marseille; Francia. Inserm; Francia. Aix-Marseille Université; Francia
description Pancreatic ductal adenocarcinoma (PDAC) has the lowest survival rate of all cancers and shows remarkable resistance to cell stress. Nuclear protein 1 (Nupr1), which mediates stress response in the pancreas, is frequently upregulated in pancreatic cancer. Here, we report that Nupr1 plays an essential role in pancreatic tumorigenesis. In a mouse model of pancreatic cancer with constitutively expressed oncogenic KrasG12D, we found that loss of Nupr1 protected from the development of pancreatic intraepithelial neoplasias (PanINs). Further, in cultured pancreatic cells, nutrient deprivation activated Nupr1 expression, which we found to be required for cell survival. We found that Nupr1 protected cells from stress-induced death by inhibiting apoptosis through a pathway dependent on transcription factor RelB and immediate early response 3 (IER3). NUPR1, RELB, and IER3 proteins were coexpressed in mouse PanINs from KrasG12D-expressing pancreas. Moreover, pancreasspecific deletion of Relb in a KrasG12D background resulted in delayed in PanIN development associated with a lack of IER3 expression. Thus, efficient PanIN formation was dependent on the expression of Nupr1 and Relb, with likely involvement of IER3. Finally, in patients with PDAC, expression of NUPR1, RELB, and IER3 was significantly correlated with a poor prognosis. Cumulatively, these results reveal a NUPR1/RELB/IER3 stress-related pathway that is required for oncogenic KrasG12D-dependent transformation of the pancreas.
publishDate 2012
dc.date.none.fl_str_mv 2012-06
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/11336/216511
Hamidi, Tewfik; Algül, Hana; Cano, Carla Eliana; Sandi, Maria José; Molejon, Maria Ines; et al.; Nuclear protein 1 promotes pancreatic cancer development and protects cells from stress by inhibiting apoptosis; American Society for Clinical Investigation; Journal of Clinical Investigation; 122; 6; 6-2012; 2092-2103
0021-9738
CONICET Digital
CONICET
url http://hdl.handle.net/11336/216511
identifier_str_mv Hamidi, Tewfik; Algül, Hana; Cano, Carla Eliana; Sandi, Maria José; Molejon, Maria Ines; et al.; Nuclear protein 1 promotes pancreatic cancer development and protects cells from stress by inhibiting apoptosis; American Society for Clinical Investigation; Journal of Clinical Investigation; 122; 6; 6-2012; 2092-2103
0021-9738
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1172/jci60144
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366404/
info:eu-repo/semantics/altIdentifier/url/https://www.jci.org/articles/view/60144
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 American Society for Clinical Investigation
publisher.none.fl_str_mv American Society for Clinical Investigation
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
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score 13.22299

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