TY - JOUR
T1 - Ectopic nerve growth factor prevents proliferation in glioma cells by senescence induction
AU - Meco, Daniela
AU - Di Francesco, Angela Maria
AU - Melotti, Linda
AU - Ruggiero, Antonio
AU - Riccardi, Riccardo
PY - 2019
Y1 - 2019
N2 - OBJECTIVE:\r\nThe neurotrophin nerve growth factor (NGF) affects survival, regulation and differentiation of both central and peripheral nervous system neurons. NGF exerts its effects primarily through tropomyosin receptor kinase A (TrkA), inducing a cascade of tyrosine kinase-initiated responses. In spite of its importance, the general behavior of NGF looks contradictory: its effects can be both stimulatory and inhibitory. The present study aims to explore the molecular mechanisms induced by NGF in glioma cancer cells.\r\n\r\nMETHODS:\r\nThe effects of NGF were investigated in high grade glioma and low grade pediatric glioma (PLGG) cell lines through comparative studies. In particular, we investigated TrkA-mediated cellular pathways, molecular signaling, proliferation, cell cycle and cellular senescence.\r\n\r\nRESULTS:\r\nWe found that exposure of PLGG cells to NGF produced stable growth arrest with the features of a senescence phenotype but without the expression of anti-poly(ADP-ribose) polymerase cleavage, a marker of apoptosis. Moreover, NGF treatment promoted the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2), signal transducer and activator of transcription 3 (STAT3), and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling. In addition, K252a, a TrkA inhibitor, significantly reduced the phosphorylation of the aforementioned signaling pathways, suggesting that NGF-activated ERK1/2 and AKT signaling take place downstream of TrkA-neurotrophin interaction.\r\n\r\nCONCLUSIONS:\r\nThese findings provide the first evidence that NGF can induce senescence of PLGG cells in a receptor-mediated fashion, thus supporting the hypothesis that in the clinical setting NGF might be beneficial to pediatric glioma patients.
AB - OBJECTIVE:\r\nThe neurotrophin nerve growth factor (NGF) affects survival, regulation and differentiation of both central and peripheral nervous system neurons. NGF exerts its effects primarily through tropomyosin receptor kinase A (TrkA), inducing a cascade of tyrosine kinase-initiated responses. In spite of its importance, the general behavior of NGF looks contradictory: its effects can be both stimulatory and inhibitory. The present study aims to explore the molecular mechanisms induced by NGF in glioma cancer cells.\r\n\r\nMETHODS:\r\nThe effects of NGF were investigated in high grade glioma and low grade pediatric glioma (PLGG) cell lines through comparative studies. In particular, we investigated TrkA-mediated cellular pathways, molecular signaling, proliferation, cell cycle and cellular senescence.\r\n\r\nRESULTS:\r\nWe found that exposure of PLGG cells to NGF produced stable growth arrest with the features of a senescence phenotype but without the expression of anti-poly(ADP-ribose) polymerase cleavage, a marker of apoptosis. Moreover, NGF treatment promoted the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2), signal transducer and activator of transcription 3 (STAT3), and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling. In addition, K252a, a TrkA inhibitor, significantly reduced the phosphorylation of the aforementioned signaling pathways, suggesting that NGF-activated ERK1/2 and AKT signaling take place downstream of TrkA-neurotrophin interaction.\r\n\r\nCONCLUSIONS:\r\nThese findings provide the first evidence that NGF can induce senescence of PLGG cells in a receptor-mediated fashion, thus supporting the hypothesis that in the clinical setting NGF might be beneficial to pediatric glioma patients.
KW - cellular senescence
KW - glioma cell lines
KW - nerve growth factor (NGF)
KW - neurotrophin
KW - cellular senescence
KW - glioma cell lines
KW - nerve growth factor (NGF)
KW - neurotrophin
UR - https://publicatt.unicatt.it/handle/10807/148168
UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85056307546&origin=inward
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85056307546&origin=inward
U2 - 10.1002/jcp.27430
DO - 10.1002/jcp.27430
M3 - Article
SN - 1097-4652
VL - 234
SP - 6820
EP - 6830
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
IS - 5
ER -