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

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

doi:10.1038/s42003-021-02258-z

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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 show all authors [1 - 20]
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.
Identifiers		DOI: 10.1038/s42003-021-02258-z PMID: 34112916
Full text		Article (Published version) (4.6 MB) - Free access Supplemental data (265.9 MB) - Free access Supplemental data (260 Kb) - Free access Other version: http://www.nature.com/articles/s42003-021-02258-z Dataset: https://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/geo/query/acc.cgi?acc=GSE173784
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme
Research groups		Immunothérapie des cancers (42) Radicaux libres et cellules souches embryonnaires (60) Voies de signalisation oncogéniques (998)
Citation (ISO format)		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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Macropinocytosis requires Gal-3 in a subset of patient-derived glioblastoma stem cells