| Title: |
Macropinocytosis requires Gal-3 in a subset of patient-derived glioblastoma stem cells |
| Authors: |
Seguin, Laetitia; Odouard, Soline; Corlazzoli, Francesca; Al Haddad, Sarah; Moindrot, Laurine; Calvo Tardon, Marta; Yebra, Mayra; Koval, Alexey; Marinari, Eliana; Bes, Viviane; Guerin, Alexandre; Allard, Mathilde Camille; Ilmjarv, Sten; Katanaev, Vladimir; Walker, Paul Richard; Krause, Karl-Heinz; Dutoit Vallotton, Valérie; Sarkaria, Jann N.; Dietrich, Pierre-Yves; Cosset, Erika |
| Source: |
ISSN: 2399-3642 ; Communications Biology, vol. 4, no. 1 (2021) 718. |
| Publication Year: |
2021 |
| Collection: |
Université de Genève: Archive ouverte UNIGE |
| Subject Terms: |
info:eu-repo/classification/ddc/612; info:eu-repo/classification/ddc/616; info:eu-repo/classification/ddc/616.07 |
| 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-3high 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/34112916; info:eu-repo/semantics/dataset/url/https://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/geo/query/acc.cgi?acc=GSE173784; unige:152352 |
| Availability: |
https://archive-ouverte.unige.ch/unige:152352 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.39F64952 |
| Database: |
BASE |