Publication: Oncogenic dependence of glioma cells on kish/TMEM167A regulation of vesicular trafficking
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Identifiers
Publication date
2019
Authors
Portela, Marta
Segura-Collar, Berta ISCIII
Argudo, Irene
Sáiz, Almudena
Gargini, Ricardo ISCIII
Sánchez-Gómez, Pilar ISCIII
Casas-Tintó, Sergio
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
Wiley
Abstract
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.
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MeSH Terms
Animals Animals, Genetically Modified Brain Brain Neoplasms Cell Line, Tumor Disease Models, Animal Drosophila Proteins Drosophila melanogaster Enzyme Inhibitors ErbB Receptors Female Gene Expression Regulation, Neoplastic Glioma Heterografts Humans Leupeptins Luminescent Proteins Male Mice Protein Transport RNA Interference
DeCS Terms
Bibliographic citation
Glia . 2019 Feb;67(2):404-417