Therapeutic advantage of targeting lysosomal membrane integrity supported by lysophagy in malignant glioma.

ABSTRACT: Lysosomes function as the digestive system of a cell and are involved in macromolecular recycling, vesicle trafficking, metabolic reprogramming, and progrowth signaling. Although quality control of lysosome biogenesis is thought to be a potential target for cancer therapy, practical strategies have not been established. Here, we show that lysosomal membrane integrity supported by lysophagy, a selective autophagy for damaged lysosomes, is a promising therapeutic target for glioblastoma (GBM). In this study, we found that ifenprodil, an FDA-approved drug with neuromodulatory activities, efficiently inhibited spheroid formation of patient-derived GBM cells in a combination with autophagy inhibition. Ifenprodil increased intracellular Ca²⁺ level, resulting in mitochondrial reactive

SUBMITTER: Jing Y 

PROVIDER: S-EPMC9357661 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature