TY - JOUR
T1 - Rapamycin promotes differentiation increasing βIII-tubulin, NeuN, and NeuroD while suppressing nestin expression in glioblastoma cells
AU - Ferrucci, Michela
AU - Biagioni, Francesca
AU - Lenzi, Paola
AU - Gambardella, Stefano
AU - Ferese, Rosangela
AU - Calierno, Maria Teresa
AU - Falleni, Alessandra
AU - Grimaldi, Alfonso
AU - Frati, Alessandro
AU - Esposito, Vincenzo
AU - Limatola, Cristina
AU - Fornai, Francesco
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Glioblastoma cells feature mammalian target of rapamycin (mTOR) up-regulation which relates to a variety of effects such as: lower survival, higher infiltration, high stemness and radio- and chemo-resistance. Recently, it was demonstrated that mTOR may produce a gene shift leading to altered protein expression. Therefore, in the present study we administered different doses of the mTOR inhibitor rapamycin to explore whether the transcription of specific genes are modified. By using a variety of methods we demonstrate that rapamycin stimulates gene transcription related to neuronal differentiation while inhibiting stemness related genes such as nestin. In these experimental conditions, cell phenotype shifts towards a pyramidal neuron-like shape owing long branches. Rapamycin suppressed cell migration when exposed to fetal bovine serum (FBS) while increasing the cell adhesion protein phospho-FAK (pFAK). The present study improves our awareness of basic mechanisms which relate mTOR activity to the biology of glioblastoma cells. These findings apply to a variety of effects which can be induced by mTOR regulation in the brain. In fact, the ability to promote neuronal differentiation might be viewed as a novel therapeutic pathway to approach neuronal regeneration.
AB - Glioblastoma cells feature mammalian target of rapamycin (mTOR) up-regulation which relates to a variety of effects such as: lower survival, higher infiltration, high stemness and radio- and chemo-resistance. Recently, it was demonstrated that mTOR may produce a gene shift leading to altered protein expression. Therefore, in the present study we administered different doses of the mTOR inhibitor rapamycin to explore whether the transcription of specific genes are modified. By using a variety of methods we demonstrate that rapamycin stimulates gene transcription related to neuronal differentiation while inhibiting stemness related genes such as nestin. In these experimental conditions, cell phenotype shifts towards a pyramidal neuron-like shape owing long branches. Rapamycin suppressed cell migration when exposed to fetal bovine serum (FBS) while increasing the cell adhesion protein phospho-FAK (pFAK). The present study improves our awareness of basic mechanisms which relate mTOR activity to the biology of glioblastoma cells. These findings apply to a variety of effects which can be induced by mTOR regulation in the brain. In fact, the ability to promote neuronal differentiation might be viewed as a novel therapeutic pathway to approach neuronal regeneration.
KW - Gerotarget
KW - Mammalian target of rapamycin
KW - Neuronal differentiation
KW - QRT-PCR
KW - Stem cells
KW - Transmission electron microscopy
UR - http://www.scopus.com/inward/record.url?scp=85018944891&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85018944891&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.15906
DO - 10.18632/oncotarget.15906
M3 - Article
AN - SCOPUS:85018944891
VL - 8
SP - 29574
EP - 29599
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 18
ER -