RT Journal Article
T1 mTOR inhibition leads to Src-Mediated EGFR internalisation and degradation in glioma cells
A1 Colella, Barbara
A1 Colardo, Mayra
A1 Iannone, Gianna
A1 Contadini, Claudia
A1 Saiz Ladera, Cristina
A1 Fuoco, Claudia
A1 Barilà, Daniela
A1 Velasco Díez, Guillermo
A1 Segatto, Marco
A1 Di Bartolomeo, Sabrina
AB 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.
PB MDPI
SN Electronic: 2072-6694
YR 2020
FD 2020-08-13
LK https://hdl.handle.net/20.500.14352/7940
UL https://hdl.handle.net/20.500.14352/7940
LA eng
NO Instituto de Salud Carlos III/Fondo Europeo de Desarrollo Regional (FEDER)
NO Italian Ministry of University and Research
NO Italian Ministry of Health
NO Associazione Italiana per la Ricerca sul Cancro (AIRC)
DS Docta Complutense
RD 8 abr 2025