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Macropinocytosis requires Gal-3 in a subset of patient-derived glioblastoma stem cells

Seguin, Laetitia
Yebra, Mayra
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Published in Communications biology. 2021, vol. 4, no. 1, 718
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.
PMID: 34112916
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Research groups Immunothérapie des cancers (42)
Radicaux libres et cellules souches embryonnaires (60)
Voies de signalisation oncogéniques (998)
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SEGUIN, Laetitia et al. Macropinocytosis requires Gal-3 in a subset of patient-derived glioblastoma stem cells. In: Communications Biology, 2021, vol. 4, n° 1, p. 718. doi: 10.1038/s42003-021-02258-z https://archive-ouverte.unige.ch/unige:152352

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Deposited on : 2021-06-14

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