2026-06-14T03:29:58Zhttps://repisalud.isciii.es/rest/oai/request

oai: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

00925njm 22002777a 4500 dc 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 author 2020-01-14 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. Cancers (Basel). 2020 Jan 14;12(1). pii: E208. 10.3390/cancers12010208 2072-6694 Cancers 31947645 http://hdl.handle.net/20.500.12105/9083 EGFR/AKT signaling Autophagy Glioma Mutant p53 Vesicular trafficking Wild-type p53 The EGFR-TMEM167A-p53 Axis Defines the Aggressiveness of Gliomas