BDNF/TrkB Signaling as a Potential Novel Target in Pediatric Brain Tumors: Anticancer Activity of Selective TrkB Inhibition in Medulloblastoma Cells

Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Deregulation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling has been associated with increased proliferative capabilities, invasiveness, and chemoresistance in several types of cancer....

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Bibliographic Details
Published in:Journal of molecular neuroscience 2016-07, Vol.59 (3), p.326-333
Main Authors: Thomaz, Amanda, Jaeger, Mariane, Buendia, Marienela, Bambini-Junior, Victorio, Gregianin, Lauro José, Brunetto, Algemir Lunardi, Brunetto, André T., de Farias, Caroline Brunetto, Roesler, Rafael
Format: Article
Language:English
Subjects:
Anticancer properties
Antineoplastic Agents - pharmacology
Antitumor activity
Azepines - pharmacology
Benzamides - pharmacology
Benzothiophene
Biomedical and Life Sciences
Biomedicine
Brain
Brain cancer
Brain Neoplasms - metabolism
Brain tumors
Brain-derived neurotrophic factor
Brain-Derived Neurotrophic Factor - pharmacology
Cancer
Carbonyls
Cell Biology
Cell Line, Tumor
Cell Proliferation - drug effects
Cell survival
Cell Survival - drug effects
Chemoresistance
Deregulation
Humans
Inhibition
Invasiveness
Medulloblastoma
Medulloblastoma - metabolism
Membrane Glycoproteins - antagonists & inhibitors
Membrane Glycoproteins - genetics
Membrane Glycoproteins - metabolism
Neurochemistry
Neurology
Neurosciences
Pediatrics
Protein Kinase Inhibitors - pharmacology
Protein-Tyrosine Kinases - antagonists & inhibitors
Protein-Tyrosine Kinases - genetics
Protein-Tyrosine Kinases - metabolism
Proteomics
Receptor, trkB
Signal Transduction
Signaling
Subgroups
TrkB receptors
Tropomyosin
Tumors
Viability
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Description
Summary:Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Deregulation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling has been associated with increased proliferative capabilities, invasiveness, and chemoresistance in several types of cancer. However, the relevance of this pathway in MB remains unknown. Here, we show that the selective TrkB inhibitor N-[2-[[(hexahydro-2-oxo-1H-azepin-3-yl)amino]carbonyl]phenyl]-benzo[b]thiophene-2-carboxamide (ANA-12) markedly reduced the viability and survival of human cell lines representative of different MB molecular subgroups. These findings provide the first evidence supporting further investigation of TrkB inhibition as a potential novel strategy for MB treatment.
ISSN:0895-8696
1559-1166
DOI:10.1007/s12031-015-0689-0