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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/216511
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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 Técnicas2025-09-29T10:27:38Zoai: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:34982025-09-29 10:27:38.846CONICET 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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1844614278578962432 |
score |
13.070432 |