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In this study, we aimed to investigate the specific metabolic features of Glioblastoma stem cells (GSC), a rare tumor subpopulation involved in tumor growth and therapy resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted comprehensive analyses of primary patient-derived GBM cultures and GSC-enriched cultures of human GBM cell lines using state-of-the-art molecular, metabolic, and phenotypic studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We showed that GSC-enriched cultures display distinct glycolytic profiles compared with differentiated tumor cells. Further analysis revealed that GSC relies on pyruvate carboxylase (PC) activity for survival and self-renewal capacity. Interestingly, inhibition of PC led to GSC death, particularly when the glutamine pool was low, and increased differentiation. Finally, while GSC displayed resistance to the chemotherapy drug etoposide, genetic or pharmacological inhibition of PC restored etoposide sensitivity in GSC, both in vitro and in orthotopic murine models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings demonstrate the critical role of PC in GSC metabolism, survival, and escape to etoposide. They also highlight PC as a therapeutic target to overcome therapy resistance in GBM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noae106","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T06:41:52Z","timestamp":1718347312000},"page":"1572-1586","source":"Crossref","is-referenced-by-count":29,"title":["Metabolic profiling of glioblastoma stem cells reveals pyruvate carboxylase as a critical survival factor and potential therapeutic target"],"prefix":"10.1093","volume":"26","author":[{"given":"Oph\u00e9lie","family":"Renoult","sequence":"first","affiliation":[{"name":"Nantes Universit\u00e9, Inserm 1307, CNRS 6075, Universit\u00e9 d\u2019Angers , Nantes ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Laurent--Blond","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, Inserm 1307, CNRS 6075, Universit\u00e9 d\u2019Angers , Nantes 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