2026-06-30T00:03:35Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/107872025-06-09T08:15:28Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19617
Repisalud
author
Portela, Marta
author
Segura-Collar, Berta
author
Argudo, Irene
author
Sáiz, Almudena
author
Gargini, Ricardo
author
Sánchez-Gómez, Pilar
author
Casas-Tinto, Sergio
funder
Ministerio de Economía y Competitividad (España)
funder
Ministerio de Ciencia e Innovación (España)
funder
Asociación Española Contra el Cáncer
2020-07-16T09:32:33Z
2020-07-16T09:32:33Z
2019
Glia . 2019 Feb;67(2):404-417
10.1002/glia.23551
1098-1136
Glia
30506943
http://hdl.handle.net/20.500.12105/10787
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.
eng
Oncogenic dependence of glioma cells on kish/TMEM167A regulation of vesicular trafficking
preprint
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URL
https://repisalud.isciii.es/bitstreams/72c5a793-a8fd-48b1-bd31-3fb8426f747c/download
File
MD5
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application/pdf
OncogenicAddictionOfGlioma.pdf
URL
https://repisalud.isciii.es/bitstreams/54961c9f-1da5-4b02-9ce1-f9f036a5f545/download
File
MD5
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text/plain
OncogenicAddictionOfGlioma.pdf.txt