The EGFR-TMEM167A-p53 Axis Defines the Aggressiveness of Gliomas

摘要: 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 these two genes. We found that wild-type p53 gliomas are more aggressive than mutant counterparts, probably because former accumulate amplifications and/or show stronger activation this receptor. In addition, identified series genes associated with vesicular trafficking gliomas. Among genes, TMEM167A showed strongest implication overall survival group tumors. agreement observation, inhibition expression impaired subcutaneous intracranial growth regardless presence mutations. absence mutations, knockdown reduced acidification intracellular vesicles, affecting autophagy process impairing signaling. This effect was mimicked by an inhibitor vacuolar ATPase. propose increased aggressiveness might be due to increase factor signaling activity, which depends on regulation TMEM167A.