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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/40898
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oai:ri.conicet.gov.ar:11336/40898 |
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CONICET Digital (CONICET) |
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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 Técnicas2025-09-29T09:34:15Zoai: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:34982025-09-29 09:34:15.331CONICET 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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1844613058715975680 |
score |
13.070432 |