Article
Reference
Macropinocytosis requires Gal-3 in a subset of patient-derived glioblastoma stem cells
SEGUIN, Laetitia, et al.
Abstract
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.
SEGUIN, Laetitia, et al . Macropinocytosis requires Gal-3 in a subset of patient-derived glioblastoma stem cells. Communications Biology , 2021, vol. 4, no. 1, p. 718
PMID : 34112916
DOI : 10.1038/s42003-021-02258-z
Available at:
http://archive-ouverte.unige.ch/unige:152352
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