PMID- 26022108
OWN - NLM
STAT- MEDLINE
DCOM- 20160815
LR  - 20220129
IS  - 1878-0261 (Electronic)
IS  - 1574-7891 (Print)
IS  - 1574-7891 (Linking)
VI  - 9
IP  - 8
DP  - 2015 Oct
TI  - Autophagy induction impairs migration and invasion by reversing EMT in 
      glioblastoma cells.
PG  - 1612-25
LID - S1574-7891(15)00114-3 [pii]
LID - 10.1016/j.molonc.2015.04.016 [doi]
AB  - Cell migration and invasion are highly regulated processes involved in both 
      physiological and pathological conditions. Here we show that autophagy modulation 
      regulates the migration and invasion capabilities of glioblastoma (GBM) cells. We 
      observed that during autophagy occurrence, obtained by nutrient deprivation or by 
      pharmacological inhibition of the mTOR complexes, GBM migration and 
      chemokine-mediated invasion were both impaired. We also observed that SNAIL and 
      SLUG, two master regulators of the epithelial-mesenchymal transition (EMT 
      process), were down-regulated upon autophagy stimulation and, as a consequence, 
      we found a transcriptional and translational up-regulation of N- and R-cadherins. 
      Conversely, in BECLIN 1-silenced GBM cells, an increased migration capability and 
      an up-regulation of SNAIL and SLUG was observed, with a resulting decrease in N- 
      and R-cadherin mRNAs. ATG5 and ATG7 down-regulation also resulted in an increased 
      migration and invasion of GBM cells combined to an up-regulation of the two EMT 
      regulators. Finally, experiments performed in primary GBM cells from patients 
      largely confirmed the results obtained in established cell cultures. Overall, our 
      results indicate that autophagy modulation triggers a molecular switch from a 
      mesenchymal phenotype to an epithelial-like one in GBM cellular models. Since the 
      aggressiveness and lethality of GBM is defined by local invasion and resistance 
      to chemotherapy, we believe that our evidence provides a further rationale for 
      including autophagy/mTOR-based targets in the current therapeutical regimen of 
      GBM patients.
CI  - Copyright (c) 2015 Federation of European Biochemical Societies. Published by 
      Elsevier B.V. All rights reserved.
FAU - Catalano, Myriam
AU  - Catalano M
AD  - Istituto Pasteur-Fondazione Cenci Bolognetti and Department of Physiology and 
      Pharmacology, Sapienza University of Rome, Italy; Neuromed IRCCS, Via Atinese, 
      Pozzilli, Italy.
FAU - D'Alessandro, Giuseppina
AU  - D'Alessandro G
AD  - Istituto Pasteur-Fondazione Cenci Bolognetti and Department of Physiology and 
      Pharmacology, Sapienza University of Rome, Italy; Neuromed IRCCS, Via Atinese, 
      Pozzilli, Italy.
FAU - Lepore, Francesca
AU  - Lepore F
AD  - Department of Biology, University of Rome Tor Vergata, Rome, Italy.
FAU - Corazzari, Marco
AU  - Corazzari M
AD  - Department of Biology, University of Rome Tor Vergata, Rome, Italy; IRCCS L. 
      Spallanzani, Rome, Italy.
FAU - Caldarola, Sara
AU  - Caldarola S
AD  - Department of Biology, University of Rome Tor Vergata, Rome, Italy.
FAU - Valacca, Cristina
AU  - Valacca C
AD  - Department of Neuroscience, IRCCS Santa Lucia Foundation, Rome, Italy.
FAU - Faienza, Fiorella
AU  - Faienza F
AD  - Department of Biology, University of Rome Tor Vergata, Rome, Italy.
FAU - Esposito, Vincenzo
AU  - Esposito V
AD  - Neuromed IRCCS, Via Atinese, Pozzilli, Italy.
FAU - Limatola, Cristina
AU  - Limatola C
AD  - Istituto Pasteur-Fondazione Cenci Bolognetti and Department of Physiology and 
      Pharmacology, Sapienza University of Rome, Italy; Neuromed IRCCS, Via Atinese, 
      Pozzilli, Italy.
FAU - Cecconi, Francesco
AU  - Cecconi F
AD  - Department of Biology, University of Rome Tor Vergata, Rome, Italy; Department of 
      Neuroscience, IRCCS Santa Lucia Foundation, Rome, Italy; Unit of Cell Stress and 
      Survival, Danish Cancer Society Research Center, 2100 Copenhagen, Denmark.
FAU - Di Bartolomeo, Sabrina
AU  - Di Bartolomeo S
AD  - Department of Biology, University of Rome Tor Vergata, Rome, Italy; Department of 
      Neuroscience, IRCCS Santa Lucia Foundation, Rome, Italy. Electronic address: 
      sabrina.dibartolomeo@uniroma2.it.
LA  - eng
GR  - GGP10225/TI_/Telethon/Italy
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150513
PL  - United States
TA  - Mol Oncol
JT  - Molecular oncology
JID - 101308230
RN  - 0 
      (1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo(h)(1,6)naphthyridin-2(1H)-one)
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (Leupeptins)
RN  - 0 (Naphthyridines)
RN  - 886U3H6UFF (Chloroquine)
RN  - RF1P63GW3K (benzyloxycarbonylleucyl-leucyl-leucine aldehyde)
SB  - IM
MH  - Animals
MH  - Autophagy/drug effects/*physiology
MH  - Cell Line, Tumor
MH  - *Cell Movement/drug effects
MH  - Chloroquine/pharmacology
MH  - Culture Media, Serum-Free/pharmacology
MH  - *Epithelial-Mesenchymal Transition/drug effects
MH  - Glioblastoma/*pathology
MH  - Humans
MH  - Leupeptins/pharmacology
MH  - Mice
MH  - Naphthyridines/pharmacology
MH  - Neoplasm Invasiveness
MH  - Up-Regulation/drug effects
PMC - PMC5528793
OTO - NOTNLM
OT  - Autophagy
OT  - Cell migration
OT  - EMT
OT  - Glioma
EDAT- 2015/05/30 06:00
MHDA- 2016/08/16 06:00
PMCR- 2015/10/01
CRDT- 2015/05/30 06:00
PHST- 2015/04/02 00:00 [received]
PHST- 2015/04/29 00:00 [revised]
PHST- 2015/04/30 00:00 [accepted]
PHST- 2015/05/30 06:00 [entrez]
PHST- 2015/05/30 06:00 [pubmed]
PHST- 2016/08/16 06:00 [medline]
PHST- 2015/10/01 00:00 [pmc-release]
AID - S1574-7891(15)00114-3 [pii]
AID - MOL22015981612 [pii]
AID - 10.1016/j.molonc.2015.04.016 [doi]
PST - ppublish
SO  - Mol Oncol. 2015 Oct;9(8):1612-25. doi: 10.1016/j.molonc.2015.04.016. Epub 2015 
      May 13.