2026-06-14T10:37:34Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/90832025-06-26T11:08:19Zcom_20.500.12105_15322com_20.500.12105_2051com_20.500.12105_2052col_20.500.12105_16938col_20.500.12105_19616col_20.500.12105_19617
Repisalud
author
Segura-Collar, Berta
author
Gargini, Ricardo
author
Tovar-Ambel, Elena
author
Hernandez-SanMiguel, Esther
author
Epifano, Carolina
author
Perez de Castro, Ignacio
author
Hernández-Laín, Aurelio
author
Casas-Tinto, Sergio
author
Sánchez-Gómez, Pilar
funder
Ministerio de Economía y Competitividad (España)
funder
Asociación Española Contra el Cáncer
2020-02-12T12:24:45Z
2020-02-12T12:24:45Z
2020-01-14
Cancers (Basel). 2020 Jan 14;12(1). pii: E208.
10.3390/cancers12010208
2072-6694
Cancers
31947645
http://hdl.handle.net/20.500.12105/9083
Despite the high frequency of EGFR and TP53 genetic alterations in gliomas, little is known about their crosstalk during tumor progression. Here, we described a mutually exclusive distribution between mutations in these two genes. We found that wild-type p53 gliomas are more aggressive than their mutant counterparts, probably because the former accumulate amplifications and/or mutations in EGFR and show a stronger activation of this receptor. In addition, we identified a series of genes associated with vesicular trafficking of EGFR in p53 wild-type gliomas. Among these genes, TMEM167A showed the strongest implication in overall survival in this group of tumors. In agreement with this observation, inhibition of TMEM167A expression impaired the subcutaneous and the intracranial growth of wild-type p53 gliomas, regardless of the presence of EGFR mutations. In the absence of p53 mutations, TMEM167A knockdown reduced the acidification of intracellular vesicles, affecting the autophagy process and impairing EGFR trafficking and signaling. This effect was mimicked by an inhibitor of the vacuolar ATPase. We propose that the increased aggressiveness of wild-type p53 gliomas might be due to the increase in growth factor signaling activity, which depends on the regulation of vesicular trafficking by TMEM167A.
eng
EGFR/AKT signaling
Autophagy
Glioma
Mutant p53
Vesicular trafficking
Wild-type p53
The EGFR-TMEM167A-p53 Axis Defines the Aggressiveness of Gliomas
research article
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URL
https://repisalud.isciii.es/bitstreams/50327f32-e153-41dd-ba72-6a1cb987366d/download
File
MD5
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application/pdf
TheEGFRTMEM167AP53_2020.pdf
URL
https://repisalud.isciii.es/bitstreams/73feadb7-4033-4491-92ed-96c101da0501/download
File
MD5
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text/plain
TheEGFRTMEM167AP53_2020.pdf.txt