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mTOR inhibition leads to Src-Mediated EGFR internalisation and degradation in glioma cells

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Colella, Barbara and Colardo, Mayra and Iannone, Gianna and Contadini, Claudia and Saiz Ladera, Cristina and Fuoco, Claudia and Barilà, Daniela and Velasco Díez, Guillermo (2020) mTOR inhibition leads to Src-Mediated EGFR internalisation and degradation in glioma cells. Cancers, 12 (8). pp. 1-18. ISSN Electronic: 2072-6694

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Official URL: https://doi.org/10.3390/cancers12082266




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.


Item Type:Article
Uncontrolled Keywords:mTOR; EGFR; Glioma; Autophagy
Subjects:Medical sciences > Medicine > Oncology
Medical sciences > Biology > Cytology
Medical sciences > Biology > Biochemistry
ID Code:64566
Deposited On:22 Mar 2021 16:03
Last Modified:22 Mar 2021 17:53

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