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Updated: Oct 5, 2026

Zebrafish Model of Neuroblastoma Metastasis
Published on: March 14, 2021
TrkA signal transduction pathways in neuroblastoma
1Division of Oncology, Children's Hospital of Philadelphia, Pennsylvania 19104, USA.
Background:
Favorable neuroblastomas frequently express high levels of the TrkA receptor, and these tumors have a propensity to either differentiate or regress, but the mechanisms responsible for these two fates are unclear.
Procedure:
To study TrkA signal transduction in neuroblastoma (nb), we stably expressed wild-type TrkA and five TrkA mutants in the human nb cell line SH-SY5Y. Resulting single cell clones were characterized by TrkA mRNA and protein expression and by autophosphorylation of the receptor.
Results:
Introduction of TrkA restored nerve growth factor (NGF) responsiveness of SH-SY5Y cells, demonstrated by morphological differentiation and induction of immediate-early genes. TrkA overexpression leads to growth inhibition in the absence of NGF, whereas NGF treatment results in increased proliferation.
Conclusions:
Analysis of downstream signaling elements in mutated TrkA receptors indicates that NGF-induced differentiation is dependent on TrkA kinase activity, but several redundant pathways seem to be used farther downstream. This suggests differences from TrkA pathways identified in PC12 cells.
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