Molecular Characterization of the Dual Effect of the GPER Agonist G-1 in Glioblastoma.

Fiche publication

Date publication

novembre 2022

Journal

International journal of molecular sciences

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BAILLY Yannick , Dr DUBOIS-POT-SCHNEIDER Hélène , Dr DUMOND Hélène , Dr RECH Fabien

Tous les auteurs :
Hirtz A, Bailly Y, Rech F, Pierson J, Dumond H, Dubois-Pot-Schneider H

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/36430793

Résumé

Glioblastoma (GBM) is the most common primary brain tumor in adults. Despite conventional treatment, consisting of a chirurgical resection followed by concomitant radio-chemotherapy, the 5-year survival rate is less than 5%. Few risk factors are clearly identified, but women are 1.4-fold less affected than men, suggesting that hormone and particularly estrogen signaling could have protective properties. Indeed, a high GPER1 (G-protein-coupled estrogen receptor) expression is associated with better survival, especially in women who produce a greater amount of estrogen. Therefore, we addressed the anti-tumor effect of the GPER agonist G-1 in vivo and characterized its molecular mechanism of action in vitro. First, the antiproliferative effect of G-1 was confirmed in a model of xenografted nude mice. A transcriptome analysis of GBM cells exposed to G-1 was performed, followed by functional analysis of the differentially expressed genes. Lipid and steroid synthesis pathways as well as cell division processes were both affected by G-1, depending on the dose and duration of the treatment. ANGPTL4, the first marker of G-1 exposure in GBM, was identified and validated in primary GBM cells and patient samples. These data strongly support the potential of G-1 as a promising chemotherapeutic compound for the treatment of GBM.