Suppression of MicroRNA-9 by Mutant EGFR signaling upregulates FOXP1 to enhance glioblastoma tumorigenicity

German G. Gomez, Stefano Volinia, Carlo M. Croce, Ciro Zanca, Ming Li, Ryan Emnett, David H. Gutmann, Cameron W. Brennan, Frank B. Furnari, Webster K. Cavenee

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

The EGF receptor (EGFR) is amplified and mutated in glioblastoma, in which its common mutation (DEGFR, also called EGFRvIII) has a variety of activities that promote growth and inhibit death, thereby conferring a strong tumor-enhancing effect. This range of activities suggested to us that DEGFR might exert its influence through pleiotropic effectors, and we hypothesized that microRNAs might serve such a function. Here, we report that DEGFR specifically suppresses one such microRNA, namely miR-9, through the Ras/PI3K/AKT axis that it is known to activate. Correspondingly, expression of miR-9 antagonizes the tumor growth advantage conferred by DEGFR. Silencing of FOXP1, a miR-9 target, inhibits DEGFR-dependent tumor growth and, conversely, derepression of FOXP1, as a consequence of miR-9 inhibition, increases tumorigenicity. FOXP1 was sufficient to increase tumor growth in the absence of oncogenic DEGFR signaling. The significance of these findings is underscored by our finding that high FOXP1 expression predicts poor survival in a cohort of 131 patients with glioblastoma. Collectively, these data suggest a novel regulatory mechanism by which DEGFR suppression of miR- 9 upregulates FOXP1 to increase tumorigenicity.

Original languageEnglish (US)
Pages (from-to)1429-1439
Number of pages11
JournalCancer Research
Volume74
Issue number5
DOIs
StatePublished - Mar 1 2014

Fingerprint Dive into the research topics of 'Suppression of MicroRNA-9 by Mutant EGFR signaling upregulates FOXP1 to enhance glioblastoma tumorigenicity'. Together they form a unique fingerprint.

  • Cite this

    Gomez, G. G., Volinia, S., Croce, C. M., Zanca, C., Li, M., Emnett, R., Gutmann, D. H., Brennan, C. W., Furnari, F. B., & Cavenee, W. K. (2014). Suppression of MicroRNA-9 by Mutant EGFR signaling upregulates FOXP1 to enhance glioblastoma tumorigenicity. Cancer Research, 74(5), 1429-1439. https://doi.org/10.1158/0008-5472.CAN-13-2117