Mitochondrial elongation and OPA1 play crucial roles during the stemness acquisition process in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer with an overall 5-year survival rate of less than 9%. The high aggressiveness of PDAC is linked to the presence of a subpopulation of cancer cells with a greater tumorigenic capacity, generically called cancer stem...

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Autores: Carmona-Carmona, Cristian Andres, Dalla Pozza, Elisa, Ambrosini, Giulia, Cisterna, Barbara, Palmieri, Marta, Decimo, Ilaria, Cuezva Marcos, José Manuel, Bottani, Emanuela, Dando, Ilaria
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/706824
Acceso en línea:http://hdl.handle.net/10486/706824
https://dx.doi.org/10.3390/cancers14143432
Access Level:acceso abierto
Palabra clave:Dynamin
Messenger RNA
Mitochondrial DNA
Small interfering RNA
Biología y Biomedicina / Biología
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spelling Mitochondrial elongation and OPA1 play crucial roles during the stemness acquisition process in pancreatic ductal adenocarcinomaCarmona-Carmona, Cristian AndresDalla Pozza, ElisaAmbrosini, GiuliaCisterna, BarbaraPalmieri, MartaDecimo, IlariaCuezva Marcos, José ManuelBottani, EmanuelaDando, IlariaDynaminMessenger RNAMitochondrial DNASmall interfering RNABiología y Biomedicina / BiologíaPancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer with an overall 5-year survival rate of less than 9%. The high aggressiveness of PDAC is linked to the presence of a subpopulation of cancer cells with a greater tumorigenic capacity, generically called cancer stem cells (CSCs). CSCs present a heterogeneous metabolic profile that might be supported by an adaptation of mitochondrial function; however, the role of this organelle in the development and maintenance of CSCs remains controversial. To determine the role of mitochondria in CSCs over longer periods, which may reflect more accurately their quiescent state, we studied the mitochondrial physiology in CSCs at short-, medium-, and long-term culture periods. We found that CSCs show a significant increase in mitochondrial mass, more mitochondrial fusion, and higher mRNA expression of genes involved in mitochondrial biogenesis than parental cells. These changes are accompanied by a regulation of the activities of OXPHOS complexes II and IV. Furthermore, the protein OPA1, which is involved in mitochondrial dynamics, is overexpressed in CSCs and modulates the tumorsphere formation. Our findings indicate that CSCs undergo mitochondrial remodeling during the stemness acquisition process, which could be exploited as a promising therapeutic target against pancreatic CSCsMDPIDepartamento de Biología MolecularFacultad de Ciencias20222022-07-02research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/706824https://dx.doi.org/10.3390/cancers14143432reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengEuropean Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 754345open accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7068242026-06-23T12:46:27Z
dc.title.none.fl_str_mv Mitochondrial elongation and OPA1 play crucial roles during the stemness acquisition process in pancreatic ductal adenocarcinoma
title Mitochondrial elongation and OPA1 play crucial roles during the stemness acquisition process in pancreatic ductal adenocarcinoma
spellingShingle Mitochondrial elongation and OPA1 play crucial roles during the stemness acquisition process in pancreatic ductal adenocarcinoma
Carmona-Carmona, Cristian Andres
Dynamin
Messenger RNA
Mitochondrial DNA
Small interfering RNA
Biología y Biomedicina / Biología
title_short Mitochondrial elongation and OPA1 play crucial roles during the stemness acquisition process in pancreatic ductal adenocarcinoma
title_full Mitochondrial elongation and OPA1 play crucial roles during the stemness acquisition process in pancreatic ductal adenocarcinoma
title_fullStr Mitochondrial elongation and OPA1 play crucial roles during the stemness acquisition process in pancreatic ductal adenocarcinoma
title_full_unstemmed Mitochondrial elongation and OPA1 play crucial roles during the stemness acquisition process in pancreatic ductal adenocarcinoma
title_sort Mitochondrial elongation and OPA1 play crucial roles during the stemness acquisition process in pancreatic ductal adenocarcinoma
dc.creator.none.fl_str_mv Carmona-Carmona, Cristian Andres
Dalla Pozza, Elisa
Ambrosini, Giulia
Cisterna, Barbara
Palmieri, Marta
Decimo, Ilaria
Cuezva Marcos, José Manuel
Bottani, Emanuela
Dando, Ilaria
author Carmona-Carmona, Cristian Andres
author_facet Carmona-Carmona, Cristian Andres
Dalla Pozza, Elisa
Ambrosini, Giulia
Cisterna, Barbara
Palmieri, Marta
Decimo, Ilaria
Cuezva Marcos, José Manuel
Bottani, Emanuela
Dando, Ilaria
author_role author
author2 Dalla Pozza, Elisa
Ambrosini, Giulia
Cisterna, Barbara
Palmieri, Marta
Decimo, Ilaria
Cuezva Marcos, José Manuel
Bottani, Emanuela
Dando, Ilaria
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Biología Molecular
Facultad de Ciencias
dc.subject.none.fl_str_mv Dynamin
Messenger RNA
Mitochondrial DNA
Small interfering RNA
Biología y Biomedicina / Biología
topic Dynamin
Messenger RNA
Mitochondrial DNA
Small interfering RNA
Biología y Biomedicina / Biología
description Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer with an overall 5-year survival rate of less than 9%. The high aggressiveness of PDAC is linked to the presence of a subpopulation of cancer cells with a greater tumorigenic capacity, generically called cancer stem cells (CSCs). CSCs present a heterogeneous metabolic profile that might be supported by an adaptation of mitochondrial function; however, the role of this organelle in the development and maintenance of CSCs remains controversial. To determine the role of mitochondria in CSCs over longer periods, which may reflect more accurately their quiescent state, we studied the mitochondrial physiology in CSCs at short-, medium-, and long-term culture periods. We found that CSCs show a significant increase in mitochondrial mass, more mitochondrial fusion, and higher mRNA expression of genes involved in mitochondrial biogenesis than parental cells. These changes are accompanied by a regulation of the activities of OXPHOS complexes II and IV. Furthermore, the protein OPA1, which is involved in mitochondrial dynamics, is overexpressed in CSCs and modulates the tumorsphere formation. Our findings indicate that CSCs undergo mitochondrial remodeling during the stemness acquisition process, which could be exploited as a promising therapeutic target against pancreatic CSCs
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-07-02
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/706824
https://dx.doi.org/10.3390/cancers14143432
url http://hdl.handle.net/10486/706824
https://dx.doi.org/10.3390/cancers14143432
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 754345
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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