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Article

mTOR Inhibition Leads to Src-Mediated EGFR Internalisation and Degradation in Glioma Cells

1
Department of Biosciences and Territory, University of Molise, 86090 Pesche (IS), Italy
2
Department of Biology, University of RomeTor Vergata, 00133 Rome, Italy
3
Laboratory of Cell Signaling, Istituto di Ricovero e Cura a carattere Scientifico (IRCSS) Fondazione Santa Lucia, 00179 Rome, Italy
4
Department of Biochemistry and Molecular Biology, School of Biology, Complutense University and Instituto de Investigaciones Sanitarias San Carlos (IdISSC), 28040 Madrid, Spain
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(8), 2266; https://doi.org/10.3390/cancers12082266
Received: 25 February 2020 / Revised: 6 August 2020 / Accepted: 11 August 2020 / Published: 13 August 2020
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. View Full-Text
Keywords: mTOR; EGFR; glioma; autophagy mTOR; EGFR; glioma; autophagy
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MDPI and ACS Style

Colella, B.; Colardo, M.; Iannone, G.; Contadini, C.; Saiz-Ladera, C.; Fuoco, C.; Barilà, D.; Velasco, G.; Segatto, M.; Di Bartolomeo, S. mTOR Inhibition Leads to Src-Mediated EGFR Internalisation and Degradation in Glioma Cells. Cancers 2020, 12, 2266. https://doi.org/10.3390/cancers12082266

AMA Style

Colella B, Colardo M, Iannone G, Contadini C, Saiz-Ladera C, Fuoco C, Barilà D, Velasco G, Segatto M, Di Bartolomeo S. mTOR Inhibition Leads to Src-Mediated EGFR Internalisation and Degradation in Glioma Cells. Cancers. 2020; 12(8):2266. https://doi.org/10.3390/cancers12082266

Chicago/Turabian Style

Colella, Barbara, Mayra Colardo, Gianna Iannone, Claudia Contadini, Cristina Saiz-Ladera, Claudia Fuoco, Daniela Barilà, Guillermo Velasco, Marco Segatto, and Sabrina Di Bartolomeo. 2020. "mTOR Inhibition Leads to Src-Mediated EGFR Internalisation and Degradation in Glioma Cells" Cancers 12, no. 8: 2266. https://doi.org/10.3390/cancers12082266

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