Decrease in Fas-induced apoptosis by the γ-secretase inhibitor is dependent on p75(NTR) in a glioblastoma cell line.

Barbara Bessette (1) , Karine Durand (1, 2) , Stéphanie Giraud (1) , Gaëlle Bégaud (1) , Muriel Mathonnet (1, 3) , Fabrice Lalloué (1)

1 HCP - Homéostasie Cellulaire et Pathologies
2 Service d'Hématologie biologique [CHU Limoges]
3 Service de Chirurgie digestive, endocrinienne et générale [CHU Limoges]

p75(NTR), a member of the tumor necrosis factor superfamily, plays a key role in numerous physiological processes, including cell survival or apoptosis. Yet, the associated signaling pathways remain poorly understood. Similar to Notch, γ-secretase cleavage is implicated in the p75(NTR) signaling pathway leading to nuclear translocation of the intracellular domain and cell death. Fas receptor activation was found to promote cell death apoptosis in several cell lines. The goal of this study was to determine the respective role of p75(NTR) and Notch in the resistance to Fas-induced apoptosis in the U-87 MG glioblastoma cell line. Using the γ-secretase inhibitor, we investigated the modulation of Fas-induced apoptosis dependent on p75(NTR)-Fas receptor interaction. Whereas the U-87 MG cells expressed the Fas receptor at the cell membrane, apoptosis induced by Fas activation was decreased by the γ-secretase inhibitor. These data suggest that γ-secretase is implicated in p75(NTR) and Fas interaction leading to cell death signaling.

Domaines: Biologie cellulaire

Barbara Bessette, Karine Durand, Stéphanie Giraud, Gaëlle Bégaud, Muriel Mathonnet, et al.. Decrease in Fas-induced apoptosis by the γ-secretase inhibitor is dependent on p75(NTR) in a glioblastoma cell line.. Experimental and Therapeutic Medicine, 2012, 3 (5), pp.873-877. ⟨10.3892/etm.2012.480⟩. ⟨hal-00872642⟩