2026-06-30T00:03:35Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/107872025-06-09T08:15:28Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19617

00925njm 22002777a 4500 dc Portela, Marta author Segura-Collar, Berta author Argudo, Irene author Sáiz, Almudena author Gargini, Ricardo author Sánchez-Gómez, Pilar author Casas-Tinto, Sergio author 2019 Genetic lesions in glioblastoma (GB) include constitutive activation of PI3K and EGFR pathways to drive cellular proliferation and tumor malignancy. An RNAi genetic screen, performed in Drosophila melanogaster to discover new modulators of GB development, identified a member of the secretory pathway: kish/TMEM167A. Downregulation of kish/TMEM167A impaired fly and human glioma formation and growth, with no effect on normal glia. Glioma cells increased the number of recycling endosomes, and reduced the number of lysosomes. In addition, EGFR vesicular localization was primed toward recycling in glioma cells. kish/TMEM167A downregulation in gliomas restored endosomal system to a physiological state and altered lysosomal function, fueling EGFR toward degradation by the proteasome. These endosomal effects mirrored the endo/lysosomal response of glioma cells to Brefeldin A (BFA), but not the Golgi disruption and the ER collapse, which are associated with the undesirable toxicity of BFA in other cancers. Our results suggest that glioma growth depends on modifications of the vesicle transport system, reliant on kish/TMEM167A. Noncanonical genes in GB could be a key for future therapeutic strategies targeting EGFR-dependent gliomas. Glia . 2019 Feb;67(2):404-417 10.1002/glia.23551 1098-1136 Glia 30506943 http://hdl.handle.net/20.500.12105/10787 Oncogenic dependence of glioma cells on kish/TMEM167A regulation of vesicular trafficking