PMID- 32823532
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231112
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 12
IP  - 8
DP  - 2020 Aug 13
TI  - mTOR Inhibition Leads to Src-Mediated EGFR Internalisation and Degradation in 
      Glioma Cells.
LID - 10.3390/cancers12082266 [doi]
LID - 2266
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.
FAU - Colella, Barbara
AU  - Colella B
AD  - Department of Biosciences and Territory, University of Molise, 86090 Pesche (IS), 
      Italy.
FAU - Colardo, Mayra
AU  - Colardo M
AD  - Department of Biosciences and Territory, University of Molise, 86090 Pesche (IS), 
      Italy.
FAU - Iannone, Gianna
AU  - Iannone G
AD  - Department of Biosciences and Territory, University of Molise, 86090 Pesche (IS), 
      Italy.
FAU - Contadini, Claudia
AU  - Contadini C
AD  - Department of Biology, University of RomeTor Vergata, 00133 Rome, Italy.
AD  - Laboratory of Cell Signaling, Istituto di Ricovero e Cura a carattere Scientifico 
      (IRCSS) Fondazione Santa Lucia, 00179 Rome, Italy.
FAU - Saiz-Ladera, Cristina
AU  - Saiz-Ladera C
AD  - Department of Biochemistry and Molecular Biology, School of Biology, Complutense 
      University and Instituto de Investigaciones Sanitarias San Carlos (IdISSC), 28040 
      Madrid, Spain.
FAU - Fuoco, Claudia
AU  - Fuoco C
AUID- ORCID: 0000-0001-8372-305X
AD  - Department of Biology, University of RomeTor Vergata, 00133 Rome, Italy.
FAU - Barila, Daniela
AU  - Barila D
AD  - Department of Biology, University of RomeTor Vergata, 00133 Rome, Italy.
AD  - Laboratory of Cell Signaling, Istituto di Ricovero e Cura a carattere Scientifico 
      (IRCSS) Fondazione Santa Lucia, 00179 Rome, Italy.
FAU - Velasco, Guillermo
AU  - Velasco G
AD  - Department of Biochemistry and Molecular Biology, School of Biology, Complutense 
      University and Instituto de Investigaciones Sanitarias San Carlos (IdISSC), 28040 
      Madrid, Spain.
FAU - Segatto, Marco
AU  - Segatto M
AUID- ORCID: 0000-0003-0465-9470
AD  - Department of Biosciences and Territory, University of Molise, 86090 Pesche (IS), 
      Italy.
FAU - Di Bartolomeo, Sabrina
AU  - Di Bartolomeo S
AUID- ORCID: 0000-0002-5748-1541
AD  - Department of Biosciences and Territory, University of Molise, 86090 Pesche (IS), 
      Italy.
LA  - eng
GR  - I2013-2016/European Regional Development Fund (ERDF)/
GR  - PI18/00442/Instituto de Salud Carlos III (ISCIII)/
GR  - FFABR/Ministero dell'Istruzione, dell'Universita e della Ricerca/
PT  - Journal Article
DEP - 20200813
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC7464593
OTO - NOTNLM
OT  - EGFR
OT  - autophagy
OT  - glioma
OT  - mTOR
COIS- The authors declare no conflict of interest.
EDAT- 2020/08/23 06:00
MHDA- 2020/08/23 06:01
PMCR- 2020/08/13
CRDT- 2020/08/23 06:00
PHST- 2020/02/25 00:00 [received]
PHST- 2020/08/06 00:00 [revised]
PHST- 2020/08/11 00:00 [accepted]
PHST- 2020/08/23 06:00 [entrez]
PHST- 2020/08/23 06:00 [pubmed]
PHST- 2020/08/23 06:01 [medline]
PHST- 2020/08/13 00:00 [pmc-release]
AID - cancers12082266 [pii]
AID - cancers-12-02266 [pii]
AID - 10.3390/cancers12082266 [doi]
PST - epublish
SO  - Cancers (Basel). 2020 Aug 13;12(8):2266. doi: 10.3390/cancers12082266.