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Macropinocytosis requires Gal-3 in a subset of patient-derived glioblastoma stem cells
Recently, we involved the carbohydrate-binding protein Galectin-3 (Gal-3) as a druggable target for KRAS-mutant-addicted lung and pancreatic cancers. Here, using glioblastoma patient-derived stem cells (GSCs), we identify and characterize a subset of Gal-3(high) glioblastoma (GBM) tumors mainly with...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192788/ https://www.ncbi.nlm.nih.gov/pubmed/34112916 http://dx.doi.org/10.1038/s42003-021-02258-z |
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author | Seguin, Laetitia Odouard, Soline Corlazzoli, Francesca Haddad, Sarah Al Moindrot, Laurine Calvo Tardón, Marta Yebra, Mayra Koval, Alexey Marinari, Eliana Bes, Viviane Guérin, Alexandre Allard, Mathilde Ilmjärv, Sten Katanaev, Vladimir L. Walker, Paul R. Krause, Karl-Heinz Dutoit, Valérie Sarkaria, Jann N. Dietrich, Pierre-Yves Cosset, Érika |
author_facet | Seguin, Laetitia Odouard, Soline Corlazzoli, Francesca Haddad, Sarah Al Moindrot, Laurine Calvo Tardón, Marta Yebra, Mayra Koval, Alexey Marinari, Eliana Bes, Viviane Guérin, Alexandre Allard, Mathilde Ilmjärv, Sten Katanaev, Vladimir L. Walker, Paul R. Krause, Karl-Heinz Dutoit, Valérie Sarkaria, Jann N. Dietrich, Pierre-Yves Cosset, Érika |
author_sort | Seguin, Laetitia |
collection | PubMed |
description | Recently, we involved the carbohydrate-binding protein Galectin-3 (Gal-3) as a druggable target for KRAS-mutant-addicted lung and pancreatic cancers. Here, using glioblastoma patient-derived stem cells (GSCs), we identify and characterize a subset of Gal-3(high) glioblastoma (GBM) tumors mainly within the mesenchymal subtype that are addicted to Gal-3-mediated macropinocytosis. Using both genetic and pharmacologic inhibition of Gal-3, we showed a significant decrease of GSC macropinocytosis activity, cell survival and invasion, in vitro and in vivo. Mechanistically, we demonstrate that Gal-3 binds to RAB10, a member of the RAS superfamily of small GTPases, and β1 integrin, which are both required for macropinocytosis activity and cell survival. Finally, by defining a Gal-3/macropinocytosis molecular signature, we could predict sensitivity to this dependency pathway and provide proof-of-principle for innovative therapeutic strategies to exploit this Achilles’ heel for a significant and unique subset of GBM patients. |
format | Online Article Text |
id | pubmed-8192788 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-81927882021-06-17 Macropinocytosis requires Gal-3 in a subset of patient-derived glioblastoma stem cells Seguin, Laetitia Odouard, Soline Corlazzoli, Francesca Haddad, Sarah Al Moindrot, Laurine Calvo Tardón, Marta Yebra, Mayra Koval, Alexey Marinari, Eliana Bes, Viviane Guérin, Alexandre Allard, Mathilde Ilmjärv, Sten Katanaev, Vladimir L. Walker, Paul R. Krause, Karl-Heinz Dutoit, Valérie Sarkaria, Jann N. Dietrich, Pierre-Yves Cosset, Érika Commun Biol Article Recently, we involved the carbohydrate-binding protein Galectin-3 (Gal-3) as a druggable target for KRAS-mutant-addicted lung and pancreatic cancers. Here, using glioblastoma patient-derived stem cells (GSCs), we identify and characterize a subset of Gal-3(high) glioblastoma (GBM) tumors mainly within the mesenchymal subtype that are addicted to Gal-3-mediated macropinocytosis. Using both genetic and pharmacologic inhibition of Gal-3, we showed a significant decrease of GSC macropinocytosis activity, cell survival and invasion, in vitro and in vivo. Mechanistically, we demonstrate that Gal-3 binds to RAB10, a member of the RAS superfamily of small GTPases, and β1 integrin, which are both required for macropinocytosis activity and cell survival. Finally, by defining a Gal-3/macropinocytosis molecular signature, we could predict sensitivity to this dependency pathway and provide proof-of-principle for innovative therapeutic strategies to exploit this Achilles’ heel for a significant and unique subset of GBM patients. Nature Publishing Group UK 2021-06-10 /pmc/articles/PMC8192788/ /pubmed/34112916 http://dx.doi.org/10.1038/s42003-021-02258-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Seguin, Laetitia Odouard, Soline Corlazzoli, Francesca Haddad, Sarah Al Moindrot, Laurine Calvo Tardón, Marta Yebra, Mayra Koval, Alexey Marinari, Eliana Bes, Viviane Guérin, Alexandre Allard, Mathilde Ilmjärv, Sten Katanaev, Vladimir L. Walker, Paul R. Krause, Karl-Heinz Dutoit, Valérie Sarkaria, Jann N. Dietrich, Pierre-Yves Cosset, Érika Macropinocytosis requires Gal-3 in a subset of patient-derived glioblastoma stem cells |
title | Macropinocytosis requires Gal-3 in a subset of patient-derived glioblastoma stem cells |
title_full | Macropinocytosis requires Gal-3 in a subset of patient-derived glioblastoma stem cells |
title_fullStr | Macropinocytosis requires Gal-3 in a subset of patient-derived glioblastoma stem cells |
title_full_unstemmed | Macropinocytosis requires Gal-3 in a subset of patient-derived glioblastoma stem cells |
title_short | Macropinocytosis requires Gal-3 in a subset of patient-derived glioblastoma stem cells |
title_sort | macropinocytosis requires gal-3 in a subset of patient-derived glioblastoma stem cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192788/ https://www.ncbi.nlm.nih.gov/pubmed/34112916 http://dx.doi.org/10.1038/s42003-021-02258-z |
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