2026-06-14T01:54:16Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/97272025-06-13T08:56:52Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19617

00925njm 22002777a 4500 dc Pozo, Natividad author Zahonero, Cristina author Fernández, Paloma author Liñares, Jose M author Ayuso, Angel author Hagiwara, Masatoshi author Pérez, Angel author Ricoy, Jose R author Hernández-Laín, Aurelio author Sepúlveda, Juan M author Sánchez-Gómez, Pilar author 2013-06 Glioblastomas (GBMs) are very aggressive tumors that are resistant to conventional chemo- and radiotherapy. New molecular therapeutic strategies are required to effectively eliminate the subpopulation of GBM tumor-initiating cells that are responsible for relapse. Since EGFR is altered in 50% of GBMs, it represents one of the most promising targets; however, EGFR kinase inhibitors have produced poor results in clinical assays, with no clear explanation for the observed resistance. We uncovered a fundamental role for the dual-specificity tyrosine phosphorylation-regulated kinase, DYRK1A, in regulating EGFR in GBMs. We found that DYRK1A was highly expressed in these tumors and that its expression was correlated with that of EGFR. Moreover, DYRK1A inhibition promoted EGFR degradation in primary GBM cell lines and neural progenitor cells, sharply reducing the self-renewal capacity of normal and tumorigenic cells. Most importantly, our data suggest that a subset of GBMs depends on high surface EGFR levels, as DYRK1A inhibition compromised their survival and produced a profound decrease in tumor burden. We propose that the recovery of EGFR stability is a key oncogenic event in a large proportion of gliomas and that pharmacological inhibition of DYRK1A could represent a promising therapeutic intervention for EGFR-dependent GBMs. J Clin Invest. 2013 Jun;123(6):2475-87. 10.1172/JCI63623 1558-8238 0021-9738 The Journal of clinical investigation 23635774 http://hdl.handle.net/20.500.12105/9727 Inhibition of DYRK1A destabilizes EGFR and reduces EGFR-dependent glioblastoma growth