Identification of a transient state during the acquisition of temozolomide resistance in glioblastoma.
Fiche publication
Date publication
janvier 2020
Journal
Cell death & disease
Auteurs
Membres identifiés du Cancéropôle Est :
Mme THIBAULT-CARPENTIER Christelle
Tous les auteurs :
Rabé M, Dumont S, Álvarez-Arenas A, Janati H, Belmonte-Beitia J, Calvo GF, Thibault-Carpentier C, Séry Q, Chauvin C, Joalland N, Briand F, Blandin S, Scotet E, Pecqueur C, Clairambault J, Oliver L, Perez-Garcia V, Nadaradjane A, Cartron PF, Gratas C, Vallette FM
Lien Pubmed
Résumé
Drug resistance limits the therapeutic efficacy in cancers and leads to tumor recurrence through ill-defined mechanisms. Glioblastoma (GBM) are the deadliest brain tumors in adults. GBM, at diagnosis or after treatment, are resistant to temozolomide (TMZ), the standard chemotherapy. To better understand the acquisition of this resistance, we performed a longitudinal study, using a combination of mathematical models, RNA sequencing, single cell analyses, functional and drug assays in a human glioma cell line (U251). After an initial response characterized by cell death induction, cells entered a transient state defined by slow growth, a distinct morphology and a shift of metabolism. Specific genes expression associated to this population revealed chromatin remodeling. Indeed, the histone deacetylase inhibitor trichostatin (TSA), specifically eliminated this population and thus prevented the appearance of fast growing TMZ-resistant cells. In conclusion, we have identified in glioblastoma a population with tolerant-like features, which could constitute a therapeutic target.
Référence
Cell Death Dis. 2020 Jan 6;11(1):19