The Cell Cycle Inhibitors p21 Cip1 and p27 Kip1 Control Proliferation but Enhance DNA Damage Resistance of Glioma Stem Cells

Autores
Morris Hanon, Olivia; Furmento, Verónica Alejandra; Rodríguez Varela, Maria Soledad; Mucci, Sofia; Fernandez Espinosa, Damian Dario; Romorini, Leonardo; Sevlever, Gustavo Emilio; Scassa, Maria Elida; Videla Richardson, Guillermo Agustín
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
High-grade gliomas are the most prevalent and lethal primary brain tumors. They display a hierarchical arrangement with a population of self-renewing and highly tumorigenic cells called cancer stemcells. These cells are thought to be responsible for tumor recurrence, which make them main candidates for targeted therapies. Unbridled cell cycle progression may explain the selective sensitivity of some cancer cells to treatments. The members of the Cip/Kip family p21Cip1 and p27Kip1 were initially considered as tumor suppressors based on their ability to block proliferation. However, they are currently looked at as proteins with dual roles in cancer: one as tumor suppressor and the other asoncogene. Therefore, the aimof this study was to determine the functions of these cell cycle inhibitors in five patientderived glioma stem cell?enriched cell lines. We found that these proteins are functional in glioma stem cells. They negatively regulate cell cycle progression both in unstressed conditions and in response to genotoxic stress. In addition, p27Kip1 is upregulated in nutrient-restricted and differentiating cells, suggesting that this Cip/Kip is a mediator of antimitogenic signals in glioma cells. Importantly, the lack of these proteins impairs cell cycle halt in response togenotoxic agents, rendering cells more vulnerable to DNA damage. For these reasons, these proteins may operate both as tumor suppressors, limiting cell proliferation, and as oncogenes, conferring cell resistance to DNA damage.Thus, deepening our knowledge on the biological functions of these Cip/Kipsmay shed light on howsomecancer cells develop drug resistance.
Fil: Morris Hanon, Olivia. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Furmento, Verónica Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Rodríguez Varela, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Mucci, Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Fernandez Espinosa, Damian Dario. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Romorini, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Sevlever, Gustavo Emilio. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Scassa, Maria Elida. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Videla Richardson, Guillermo Agustín. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Materia
Glioma Stem Cells
Dna Damage
Cell Cycle
Cip/Kip
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/40898
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/40898
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The Cell Cycle Inhibitors p21 Cip1 and p27 Kip1 Control Proliferation but Enhance DNA Damage Resistance of Glioma Stem CellsMorris Hanon, OliviaFurmento, Verónica AlejandraRodríguez Varela, Maria SoledadMucci, SofiaFernandez Espinosa, Damian DarioRomorini, LeonardoSevlever, Gustavo EmilioScassa, Maria ElidaVidela Richardson, Guillermo AgustínGlioma Stem CellsDna DamageCell CycleCip/Kiphttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3High-grade gliomas are the most prevalent and lethal primary brain tumors. They display a hierarchical arrangement with a population of self-renewing and highly tumorigenic cells called cancer stemcells. These cells are thought to be responsible for tumor recurrence, which make them main candidates for targeted therapies. Unbridled cell cycle progression may explain the selective sensitivity of some cancer cells to treatments. The members of the Cip/Kip family p21Cip1 and p27Kip1 were initially considered as tumor suppressors based on their ability to block proliferation. However, they are currently looked at as proteins with dual roles in cancer: one as tumor suppressor and the other asoncogene. Therefore, the aimof this study was to determine the functions of these cell cycle inhibitors in five patientderived glioma stem cell?enriched cell lines. We found that these proteins are functional in glioma stem cells. They negatively regulate cell cycle progression both in unstressed conditions and in response to genotoxic stress. In addition, p27Kip1 is upregulated in nutrient-restricted and differentiating cells, suggesting that this Cip/Kip is a mediator of antimitogenic signals in glioma cells. Importantly, the lack of these proteins impairs cell cycle halt in response togenotoxic agents, rendering cells more vulnerable to DNA damage. For these reasons, these proteins may operate both as tumor suppressors, limiting cell proliferation, and as oncogenes, conferring cell resistance to DNA damage.Thus, deepening our knowledge on the biological functions of these Cip/Kipsmay shed light on howsomecancer cells develop drug resistance.Fil: Morris Hanon, Olivia. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Furmento, Verónica Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Rodríguez Varela, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Mucci, Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fernandez Espinosa, Damian Dario. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Romorini, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Sevlever, Gustavo Emilio. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Scassa, Maria Elida. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Videla Richardson, Guillermo Agustín. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaElsevier2017-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/40898Morris Hanon, Olivia; Furmento, Verónica Alejandra; Rodríguez Varela, Maria Soledad; Mucci, Sofia; Fernandez Espinosa, Damian Dario; et al.; The Cell Cycle Inhibitors p21 Cip1 and p27 Kip1 Control Proliferation but Enhance DNA Damage Resistance of Glioma Stem Cells; Elsevier; Neoplasia; 19; 7; 7-2017; 519-5291476-5586CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.neo.2017.04.001info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458648/info:eu-repo/semantics/altIdentifier/url/http://www.neoplasia.com/article/S1476-5586(17)30044-1/fulltextinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:22:31Zoai:ri.conicet.gov.ar:11336/40898instacron: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 14:22:31.377CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The Cell Cycle Inhibitors p21 Cip1 and p27 Kip1 Control Proliferation but Enhance DNA Damage Resistance of Glioma Stem Cells
title The Cell Cycle Inhibitors p21 Cip1 and p27 Kip1 Control Proliferation but Enhance DNA Damage Resistance of Glioma Stem Cells
spellingShingle The Cell Cycle Inhibitors p21 Cip1 and p27 Kip1 Control Proliferation but Enhance DNA Damage Resistance of Glioma Stem Cells
Morris Hanon, Olivia
Glioma Stem Cells
Dna Damage
Cell Cycle
Cip/Kip
title_short The Cell Cycle Inhibitors p21 Cip1 and p27 Kip1 Control Proliferation but Enhance DNA Damage Resistance of Glioma Stem Cells
title_full The Cell Cycle Inhibitors p21 Cip1 and p27 Kip1 Control Proliferation but Enhance DNA Damage Resistance of Glioma Stem Cells
title_fullStr The Cell Cycle Inhibitors p21 Cip1 and p27 Kip1 Control Proliferation but Enhance DNA Damage Resistance of Glioma Stem Cells
title_full_unstemmed The Cell Cycle Inhibitors p21 Cip1 and p27 Kip1 Control Proliferation but Enhance DNA Damage Resistance of Glioma Stem Cells
title_sort The Cell Cycle Inhibitors p21 Cip1 and p27 Kip1 Control Proliferation but Enhance DNA Damage Resistance of Glioma Stem Cells
dc.creator.none.fl_str_mv Morris Hanon, Olivia
Furmento, Verónica Alejandra
Rodríguez Varela, Maria Soledad
Mucci, Sofia
Fernandez Espinosa, Damian Dario
Romorini, Leonardo
Sevlever, Gustavo Emilio
Scassa, Maria Elida
Videla Richardson, Guillermo Agustín
author Morris Hanon, Olivia
author_facet Morris Hanon, Olivia
Furmento, Verónica Alejandra
Rodríguez Varela, Maria Soledad
Mucci, Sofia
Fernandez Espinosa, Damian Dario
Romorini, Leonardo
Sevlever, Gustavo Emilio
Scassa, Maria Elida
Videla Richardson, Guillermo Agustín
author_role author
author2 Furmento, Verónica Alejandra
Rodríguez Varela, Maria Soledad
Mucci, Sofia
Fernandez Espinosa, Damian Dario
Romorini, Leonardo
Sevlever, Gustavo Emilio
Scassa, Maria Elida
Videla Richardson, Guillermo Agustín
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Glioma Stem Cells
Dna Damage
Cell Cycle
Cip/Kip
topic Glioma Stem Cells
Dna Damage
Cell Cycle
Cip/Kip
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv High-grade gliomas are the most prevalent and lethal primary brain tumors. They display a hierarchical arrangement with a population of self-renewing and highly tumorigenic cells called cancer stemcells. These cells are thought to be responsible for tumor recurrence, which make them main candidates for targeted therapies. Unbridled cell cycle progression may explain the selective sensitivity of some cancer cells to treatments. The members of the Cip/Kip family p21Cip1 and p27Kip1 were initially considered as tumor suppressors based on their ability to block proliferation. However, they are currently looked at as proteins with dual roles in cancer: one as tumor suppressor and the other asoncogene. Therefore, the aimof this study was to determine the functions of these cell cycle inhibitors in five patientderived glioma stem cell?enriched cell lines. We found that these proteins are functional in glioma stem cells. They negatively regulate cell cycle progression both in unstressed conditions and in response to genotoxic stress. In addition, p27Kip1 is upregulated in nutrient-restricted and differentiating cells, suggesting that this Cip/Kip is a mediator of antimitogenic signals in glioma cells. Importantly, the lack of these proteins impairs cell cycle halt in response togenotoxic agents, rendering cells more vulnerable to DNA damage. For these reasons, these proteins may operate both as tumor suppressors, limiting cell proliferation, and as oncogenes, conferring cell resistance to DNA damage.Thus, deepening our knowledge on the biological functions of these Cip/Kipsmay shed light on howsomecancer cells develop drug resistance.
Fil: Morris Hanon, Olivia. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Furmento, Verónica Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Rodríguez Varela, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Mucci, Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Fernandez Espinosa, Damian Dario. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Romorini, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Sevlever, Gustavo Emilio. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Scassa, Maria Elida. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Videla Richardson, Guillermo Agustín. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
description High-grade gliomas are the most prevalent and lethal primary brain tumors. They display a hierarchical arrangement with a population of self-renewing and highly tumorigenic cells called cancer stemcells. These cells are thought to be responsible for tumor recurrence, which make them main candidates for targeted therapies. Unbridled cell cycle progression may explain the selective sensitivity of some cancer cells to treatments. The members of the Cip/Kip family p21Cip1 and p27Kip1 were initially considered as tumor suppressors based on their ability to block proliferation. However, they are currently looked at as proteins with dual roles in cancer: one as tumor suppressor and the other asoncogene. Therefore, the aimof this study was to determine the functions of these cell cycle inhibitors in five patientderived glioma stem cell?enriched cell lines. We found that these proteins are functional in glioma stem cells. They negatively regulate cell cycle progression both in unstressed conditions and in response to genotoxic stress. In addition, p27Kip1 is upregulated in nutrient-restricted and differentiating cells, suggesting that this Cip/Kip is a mediator of antimitogenic signals in glioma cells. Importantly, the lack of these proteins impairs cell cycle halt in response togenotoxic agents, rendering cells more vulnerable to DNA damage. For these reasons, these proteins may operate both as tumor suppressors, limiting cell proliferation, and as oncogenes, conferring cell resistance to DNA damage.Thus, deepening our knowledge on the biological functions of these Cip/Kipsmay shed light on howsomecancer cells develop drug resistance.
publishDate 2017
dc.date.none.fl_str_mv 2017-07
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/11336/40898
Morris Hanon, Olivia; Furmento, Verónica Alejandra; Rodríguez Varela, Maria Soledad; Mucci, Sofia; Fernandez Espinosa, Damian Dario; et al.; The Cell Cycle Inhibitors p21 Cip1 and p27 Kip1 Control Proliferation but Enhance DNA Damage Resistance of Glioma Stem Cells; Elsevier; Neoplasia; 19; 7; 7-2017; 519-529
1476-5586
CONICET Digital
CONICET
url http://hdl.handle.net/11336/40898
identifier_str_mv Morris Hanon, Olivia; Furmento, Verónica Alejandra; Rodríguez Varela, Maria Soledad; Mucci, Sofia; Fernandez Espinosa, Damian Dario; et al.; The Cell Cycle Inhibitors p21 Cip1 and p27 Kip1 Control Proliferation but Enhance DNA Damage Resistance of Glioma Stem Cells; Elsevier; Neoplasia; 19; 7; 7-2017; 519-529
1476-5586
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.neo.2017.04.001
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458648/
info:eu-repo/semantics/altIdentifier/url/http://www.neoplasia.com/article/S1476-5586(17)30044-1/fulltext
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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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