Inhibition of the pseudokinase MLKL alters extracellular vesicle release and reduces tumor growth in glioblastoma - Archive ouverte HAL Access content directly
Journal Articles iScience Year : 2022

Inhibition of the pseudokinase MLKL alters extracellular vesicle release and reduces tumor growth in glioblastoma

(1, 2, 3) , (1, 3) , (3, 1) , (1, 3) , (1, 3) , (1, 3) , (1, 3) , (1, 3) , (1, 3) , (4) , (5, 6, 7) , (5, 6, 7) , (3, 8, 9) , (3, 8, 9) , (3, 8, 9) , (1, 3) , (1, 2, 3)
1
2
3
4
5
6
7
8
9

Abstract

Extracellular vesicles (EVs) are lipid-based nanosized particles that convey biological material from donor to recipient cells. EVs play key roles in glioblastoma progression because glioblastoma stem-like cells (GSCs) release pro-oncogenic, proangiogenic, and pro inflammatory EVs. However, the molecular basis of EV release remains poorly understood. Here, we report the identification of the pseudokinase MLKL, a crucial effector of cell death by necroptosis, as a regulator of the constitutive secretion of EVs in GSCs. We find that genetic, protein, and pharmacological targeting of MLKL alters intracellular trafficking and EV release, and reduces GSC expansion. Nevertheless, this function ascribed to MLKL appears independent of its role during necroptosis. In vivo, pharmacological inhibition of MLKL reduces the tumor burden and the level of plasmatic EVs. This work highlights the necroptosis-independent role of MLKL in vesicle release and suggests that interfering with EVs is a promising therapeutic option to sensitize glioblastoma cells.
Fichier principal
Vignette du fichier
1-s2.0-S2589004222013906-main.pdf (4.74 Mo) Télécharger le fichier
Origin : Publication funded by an institution

Dates and versions

inserm-03787564 , version 1 (25-09-2022)

Identifiers

Cite

Gwennan André-Grégoire, Clément Maghe, Tiphaine Douanne, Sara Rosińska, Fiorella Spinelli, et al.. Inhibition of the pseudokinase MLKL alters extracellular vesicle release and reduces tumor growth in glioblastoma. iScience, 2022, 25, pp.105118. ⟨10.1016/j.isci.2022.105118⟩. ⟨inserm-03787564⟩
38 View
4 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More