Pro-tumoral Ca signaling is dependent on Slowpoke and Ca-α1T channels in Drosophila melanogaster glioma

Ion channel-mediated cytosolic Ca oscillations play a crucial role in promoting glioblastoma growth. Here, we have studied the expression and functional roles of prospective oncogenic targets Slowpoke and Ca-α1T channels in a Drosophila melanogaster glioma model. While their mammalian orthologs have...

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Detalhes bibliográficos
Autores: Alza, Lía, Montes-Labrador, Patricia, Megías, Diego, Casali, Andreu, Casas-Tintó, Sergio, Herreros Danés, Judit, Cantí Nicolás, Carles
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2026
País:España
Recursos:Universitat de Lleida (UdL)
Repositório:Repositori Obert UdL
OAI Identifier:oai:dnet:.___________::07c9b6e72a9485b63bb1b82f616dde75
Acesso em linha:https://doi.org/10.1038/s41598-026-42712-8
https://hdl.handle.net/10459.1/470065
Access Level:Acceso aberto
Palavra-chave:Calcium
Glioma
Ion channels
Oncogenic pathways
Proliferation
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spelling Pro-tumoral Ca signaling is dependent on Slowpoke and Ca-α1T channels in Drosophila melanogaster gliomaAlza, LíaMontes-Labrador, PatriciaMegías, DiegoCasali, AndreuCasas-Tintó, SergioHerreros Danés, JuditCantí Nicolás, CarlesCalciumGliomaIon channelsOncogenic pathwaysProliferationIon channel-mediated cytosolic Ca oscillations play a crucial role in promoting glioblastoma growth. Here, we have studied the expression and functional roles of prospective oncogenic targets Slowpoke and Ca-α1T channels in a Drosophila melanogaster glioma model. While their mammalian orthologs have shown to be relevant for glioblastoma cell viability in vitro, there is no data available about their oncogenic function in a complex in vivo environment. Using RNAis against Slowpoke and Ca-α1T specifically expressed in glial cells, we show that both channels contribute to magnify Ca activity and ensuing Ca-dependent pro-tumoral pathways, glial cell proliferation and membrane extension. However, only the knockdown of Slowpoke extends the lifespan of glioma-bearing individuals and reverses glioma-induced neurodegeneration, suggesting its functional association with other Ca channels in addition to Ca-α1T. Furthermore, RNAseq transcriptomic analysis reveals that Slowpoke regulates excitatory neurotransmission, highlighting its potential as a therapeutic target in glioblastoma.This work was funded by the Spanish Ministry of Science and Innovation (Programa RETOS RTI2018-094739-B-I00 and Generación de Conocimiento PID2022-138688OB-I00 to CC and JH; PID2022-139786OB-I00 and PI22CIII/00062 to SCT, and PID2022-141323NB-I00 to AC) and by Fundació La Marató de TV3 (201909-30 to CC).Nature2026info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://doi.org/10.1038/s41598-026-42712-8https://hdl.handle.net/10459.1/470065reponame:Repositori Obert UdL instname:Universitat de Lleida (UdL)Inglés138688OBinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-138688OB-I00Reproducció del document publicat a: https://doi.org/10.1038/s41598-026-42712-8Scientific Reports, 2026, vol. 16, núm. 1cc-by-nc-nd (c)The Authors, 2026Attribution-NonCommercial-NoDerivatives 4.0 Internationalinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-nd/4.0/oai:dnet:.___________::07c9b6e72a9485b63bb1b82f616dde752026-06-24T12:42:17Z
dc.title.none.fl_str_mv Pro-tumoral Ca signaling is dependent on Slowpoke and Ca-α1T channels in Drosophila melanogaster glioma
title Pro-tumoral Ca signaling is dependent on Slowpoke and Ca-α1T channels in Drosophila melanogaster glioma
spellingShingle Pro-tumoral Ca signaling is dependent on Slowpoke and Ca-α1T channels in Drosophila melanogaster glioma
Alza, Lía
Calcium
Glioma
Ion channels
Oncogenic pathways
Proliferation
title_short Pro-tumoral Ca signaling is dependent on Slowpoke and Ca-α1T channels in Drosophila melanogaster glioma
title_full Pro-tumoral Ca signaling is dependent on Slowpoke and Ca-α1T channels in Drosophila melanogaster glioma
title_fullStr Pro-tumoral Ca signaling is dependent on Slowpoke and Ca-α1T channels in Drosophila melanogaster glioma
title_full_unstemmed Pro-tumoral Ca signaling is dependent on Slowpoke and Ca-α1T channels in Drosophila melanogaster glioma
title_sort Pro-tumoral Ca signaling is dependent on Slowpoke and Ca-α1T channels in Drosophila melanogaster glioma
dc.creator.none.fl_str_mv Alza, Lía
Montes-Labrador, Patricia
Megías, Diego
Casali, Andreu
Casas-Tintó, Sergio
Herreros Danés, Judit
Cantí Nicolás, Carles
author Alza, Lía
author_facet Alza, Lía
Montes-Labrador, Patricia
Megías, Diego
Casali, Andreu
Casas-Tintó, Sergio
Herreros Danés, Judit
Cantí Nicolás, Carles
author_role author
author2 Montes-Labrador, Patricia
Megías, Diego
Casali, Andreu
Casas-Tintó, Sergio
Herreros Danés, Judit
Cantí Nicolás, Carles
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Calcium
Glioma
Ion channels
Oncogenic pathways
Proliferation
topic Calcium
Glioma
Ion channels
Oncogenic pathways
Proliferation
description Ion channel-mediated cytosolic Ca oscillations play a crucial role in promoting glioblastoma growth. Here, we have studied the expression and functional roles of prospective oncogenic targets Slowpoke and Ca-α1T channels in a Drosophila melanogaster glioma model. While their mammalian orthologs have shown to be relevant for glioblastoma cell viability in vitro, there is no data available about their oncogenic function in a complex in vivo environment. Using RNAis against Slowpoke and Ca-α1T specifically expressed in glial cells, we show that both channels contribute to magnify Ca activity and ensuing Ca-dependent pro-tumoral pathways, glial cell proliferation and membrane extension. However, only the knockdown of Slowpoke extends the lifespan of glioma-bearing individuals and reverses glioma-induced neurodegeneration, suggesting its functional association with other Ca channels in addition to Ca-α1T. Furthermore, RNAseq transcriptomic analysis reveals that Slowpoke regulates excitatory neurotransmission, highlighting its potential as a therapeutic target in glioblastoma.
publishDate 2026
dc.date.none.fl_str_mv 2026
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 https://doi.org/10.1038/s41598-026-42712-8
https://hdl.handle.net/10459.1/470065
url https://doi.org/10.1038/s41598-026-42712-8
https://hdl.handle.net/10459.1/470065
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv 138688OB
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-138688OB-I00
Reproducció del document publicat a: https://doi.org/10.1038/s41598-026-42712-8
Scientific Reports, 2026, vol. 16, núm. 1
dc.rights.none.fl_str_mv cc-by-nc-nd (c)The Authors, 2026
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
rights_invalid_str_mv cc-by-nc-nd (c)The Authors, 2026
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Nature
publisher.none.fl_str_mv Nature
dc.source.none.fl_str_mv reponame:Repositori Obert UdL
instname:Universitat de Lleida (UdL)
instname_str Universitat de Lleida (UdL)
reponame_str Repositori Obert UdL
collection Repositori Obert UdL
repository.name.fl_str_mv
repository.mail.fl_str_mv
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