Epidermal Growth Factor receptor (EGFR) is a tyrosine kinase receptor widely expressed on the surface of numerous cell types, which activates several downstream signalling pathways involved in cell proliferation, migration and survival. EGFR alterations, such as overexpression or mutations, have been frequently observed in several cancers, including glioblastoma (GBM), and are associated to uncontrolled cell proliferation. Here we show that the inhibition of mammalian target of Rapamycin (mTOR) mediates EGFR delivery to lysosomes for degradation in GBM cells, independently of autophagy activation. Coherently with EGFR internalisation and degradation, mTOR blockade negatively affects the mitogen activated protein/extracellular signal-regulated kinase (MAPK)/ERK pathway. Furthermore, we provide evidence that Src kinase activation is required for EGFR internaliation upon mTOR inhibition. Our results further support the hypothesis that mTOR targeting may represent an effective therapeutic strategy in GBM management, as its inhibition results in EGFR degradation and in proliferative signal alteration.

Colella, B., Colardo, M., Iannone, G., Contadini, C., Saiz-Ladera, C., Fuoco, C., et al. (2020). mTOR inhibition leads to SRC-mediated EGFR internalisation and degradation in glioma cells. CANCERS, 12(8) [10.3390/cancers12082266].

mTOR inhibition leads to SRC-mediated EGFR internalisation and degradation in glioma cells

Fuoco C;Barila', D;Di Bartolomeo, S
2020-08-13

Abstract

Epidermal Growth Factor receptor (EGFR) is a tyrosine kinase receptor widely expressed on the surface of numerous cell types, which activates several downstream signalling pathways involved in cell proliferation, migration and survival. EGFR alterations, such as overexpression or mutations, have been frequently observed in several cancers, including glioblastoma (GBM), and are associated to uncontrolled cell proliferation. Here we show that the inhibition of mammalian target of Rapamycin (mTOR) mediates EGFR delivery to lysosomes for degradation in GBM cells, independently of autophagy activation. Coherently with EGFR internalisation and degradation, mTOR blockade negatively affects the mitogen activated protein/extracellular signal-regulated kinase (MAPK)/ERK pathway. Furthermore, we provide evidence that Src kinase activation is required for EGFR internaliation upon mTOR inhibition. Our results further support the hypothesis that mTOR targeting may represent an effective therapeutic strategy in GBM management, as its inhibition results in EGFR degradation and in proliferative signal alteration.
13-ago-2020
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/06 - ANATOMIA COMPARATA E CITOLOGIA
Settore BIO/18 - GENETICA
English
Con Impact Factor ISI
Glioblastoma; EGFR; SRC kinase; Autophagy
Colella, B., Colardo, M., Iannone, G., Contadini, C., Saiz-Ladera, C., Fuoco, C., et al. (2020). mTOR inhibition leads to SRC-mediated EGFR internalisation and degradation in glioma cells. CANCERS, 12(8) [10.3390/cancers12082266].
Colella, B; Colardo, M; Iannone, G; Contadini, C; Saiz-Ladera, C; Fuoco, C; Barila', D; Velasco, G; Segatto, M; Di Bartolomeo, S
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/258219
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