Impairment of Autophagic Flux Participates in the Antitumor Effects of TAT-Cx43266-283 in Glioblastoma Stem Cells

Autophagy is a physiological process by which various damaged or non-essential cytosolic components are recycled, contributing to cell survival under stress conditions. In cancer, autophagy can have antitumor or protumor effects depending on the developmental stage. Here, we use Western blotting, im...

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Autores: Gutiérrez Pelaz, Sara, Ollauri-Ibáñez, Claudia, Lillo Delgado, María Concepción, Tabernero Urbieta, María Aránzazu
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/154974
Acceso en línea:http://hdl.handle.net/10366/154974
Access Level:acceso abierto
Palabra clave:autophagy
c-Src
cell-penetrating peptide
connexin43
glioblastoma
glioblastoma stem cells
Cells
Glioblastoma
Cell-Penetrating Peptides
Proto-Oncogene Proteins pp60(c-src)
Autophagy
2490 Neurociencias
2302.21 Biología Molecular
2407 Biología Celular
id ES_24d0d63cd2a52cb8f1e585e22b3cefef
oai_identifier_str oai:gredos.usal.es:10366/154974
network_acronym_str ES
network_name_str España
repository_id_str
spelling Impairment of Autophagic Flux Participates in the Antitumor Effects of TAT-Cx43266-283 in Glioblastoma Stem CellsGutiérrez Pelaz, SaraOllauri-Ibáñez, ClaudiaLillo Delgado, María ConcepciónTabernero Urbieta, María Aránzazuautophagyc-Srccell-penetrating peptideconnexin43glioblastomaglioblastoma stem cellsCellsGlioblastomaCell-Penetrating PeptidesProto-Oncogene Proteins pp60(c-src)Autophagy2490 Neurociencias2302.21 Biología Molecular2407 Biología CelularAutophagy is a physiological process by which various damaged or non-essential cytosolic components are recycled, contributing to cell survival under stress conditions. In cancer, autophagy can have antitumor or protumor effects depending on the developmental stage. Here, we use Western blotting, immunochemistry, and transmission electron microscopy to demonstrate that the antitumor peptide TAT-Cx43266-283, a c-Src inhibitor, blocks autophagic flux in glioblastoma stem cells (GSCs) under basal and nutrient-deprived conditions. Upon nutrient deprivation, GSCs acquired a dormant-like phenotype that was disrupted by inhibition of autophagy with TAT-Cx43266-283 or chloroquine (a classic autophagy inhibitor), leading to GSC death. Remarkably, dasatinib, a clinically available c-Src inhibitor, could not replicate TAT-Cx43266-283 effect on dormant GSCs, revealing for the first time the possible involvement of pathways other than c-Src in TAT-Cx43266-283 effect. TAT-Cx43266-283 exerts an antitumor effect both in nutrient-complete and nutrient-deprived environments, which constitutes an advantage over chloroquine and dasatinib, whose effects depend on nutrient environment. Finally, our analysis of the levels of autophagy-related proteins in healthy and glioma donors suggests that autophagy is upregulated in glioblastoma, further supporting the interest in inhibiting this process in the most aggressive brain tumor and the potential use of TAT-Cx43266-283 as a therapy for this type of cancer.FEDER RTI2018-099873-B-I00/Ministerio de Ciencia e Innovación FEDER SA125P20/Junta de Castilla y León202420242021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10366/154974reponame:GREDOS. Repositorio Institucional de la Universidad de Salamancainstname:Universidad de Salamanca (USAL)Inglésinfo:eu-repo/semantics/openAccessoai:gredos.usal.es:10366/1549742026-06-07T06:28:51Z
dc.title.none.fl_str_mv Impairment of Autophagic Flux Participates in the Antitumor Effects of TAT-Cx43266-283 in Glioblastoma Stem Cells
title Impairment of Autophagic Flux Participates in the Antitumor Effects of TAT-Cx43266-283 in Glioblastoma Stem Cells
spellingShingle Impairment of Autophagic Flux Participates in the Antitumor Effects of TAT-Cx43266-283 in Glioblastoma Stem Cells
Gutiérrez Pelaz, Sara
autophagy
c-Src
cell-penetrating peptide
connexin43
glioblastoma
glioblastoma stem cells
Cells
Glioblastoma
Cell-Penetrating Peptides
Proto-Oncogene Proteins pp60(c-src)
Autophagy
2490 Neurociencias
2302.21 Biología Molecular
2407 Biología Celular
title_short Impairment of Autophagic Flux Participates in the Antitumor Effects of TAT-Cx43266-283 in Glioblastoma Stem Cells
title_full Impairment of Autophagic Flux Participates in the Antitumor Effects of TAT-Cx43266-283 in Glioblastoma Stem Cells
title_fullStr Impairment of Autophagic Flux Participates in the Antitumor Effects of TAT-Cx43266-283 in Glioblastoma Stem Cells
title_full_unstemmed Impairment of Autophagic Flux Participates in the Antitumor Effects of TAT-Cx43266-283 in Glioblastoma Stem Cells
title_sort Impairment of Autophagic Flux Participates in the Antitumor Effects of TAT-Cx43266-283 in Glioblastoma Stem Cells
dc.creator.none.fl_str_mv Gutiérrez Pelaz, Sara
Ollauri-Ibáñez, Claudia
Lillo Delgado, María Concepción
Tabernero Urbieta, María Aránzazu
author Gutiérrez Pelaz, Sara
author_facet Gutiérrez Pelaz, Sara
Ollauri-Ibáñez, Claudia
Lillo Delgado, María Concepción
Tabernero Urbieta, María Aránzazu
author_role author
author2 Ollauri-Ibáñez, Claudia
Lillo Delgado, María Concepción
Tabernero Urbieta, María Aránzazu
author2_role author
author
author
dc.subject.none.fl_str_mv autophagy
c-Src
cell-penetrating peptide
connexin43
glioblastoma
glioblastoma stem cells
Cells
Glioblastoma
Cell-Penetrating Peptides
Proto-Oncogene Proteins pp60(c-src)
Autophagy
2490 Neurociencias
2302.21 Biología Molecular
2407 Biología Celular
topic autophagy
c-Src
cell-penetrating peptide
connexin43
glioblastoma
glioblastoma stem cells
Cells
Glioblastoma
Cell-Penetrating Peptides
Proto-Oncogene Proteins pp60(c-src)
Autophagy
2490 Neurociencias
2302.21 Biología Molecular
2407 Biología Celular
description Autophagy is a physiological process by which various damaged or non-essential cytosolic components are recycled, contributing to cell survival under stress conditions. In cancer, autophagy can have antitumor or protumor effects depending on the developmental stage. Here, we use Western blotting, immunochemistry, and transmission electron microscopy to demonstrate that the antitumor peptide TAT-Cx43266-283, a c-Src inhibitor, blocks autophagic flux in glioblastoma stem cells (GSCs) under basal and nutrient-deprived conditions. Upon nutrient deprivation, GSCs acquired a dormant-like phenotype that was disrupted by inhibition of autophagy with TAT-Cx43266-283 or chloroquine (a classic autophagy inhibitor), leading to GSC death. Remarkably, dasatinib, a clinically available c-Src inhibitor, could not replicate TAT-Cx43266-283 effect on dormant GSCs, revealing for the first time the possible involvement of pathways other than c-Src in TAT-Cx43266-283 effect. TAT-Cx43266-283 exerts an antitumor effect both in nutrient-complete and nutrient-deprived environments, which constitutes an advantage over chloroquine and dasatinib, whose effects depend on nutrient environment. Finally, our analysis of the levels of autophagy-related proteins in healthy and glioma donors suggests that autophagy is upregulated in glioblastoma, further supporting the interest in inhibiting this process in the most aggressive brain tumor and the potential use of TAT-Cx43266-283 as a therapy for this type of cancer.
publishDate 2021
dc.date.none.fl_str_mv 2021
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10366/154974
url http://hdl.handle.net/10366/154974
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:GREDOS. Repositorio Institucional de la Universidad de Salamanca
instname:Universidad de Salamanca (USAL)
instname_str Universidad de Salamanca (USAL)
reponame_str GREDOS. Repositorio Institucional de la Universidad de Salamanca
collection GREDOS. Repositorio Institucional de la Universidad de Salamanca
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869404721681268736
score 15.300724

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