Unknown

Dataset Information

0

Neurotrophin-3 production promotes human neuroblastoma cell survival by inhibiting TrkC-induced apoptosis.


ABSTRACT: Tropomyosin-related kinase receptor C (TrkC) is a neurotrophin receptor with tyrosine kinase activity that was expected to be oncogenic. However, it has several characteristics of a tumor suppressor: its expression in tumors has often been associated with good prognosis; and it was recently demonstrated to be a dependence receptor, transducing different positive signals in the presence of ligand but inducing apoptosis in the absence of ligand. Here we show that the TrkC ligand neurotrophin-3 (NT-3) is upregulated in a large fraction of aggressive human neuroblastomas (NBs) and that it blocks TrkC-induced apoptosis of human NB cell lines, consistent with the idea that TrkC is a dependence receptor. Functionally, both siRNA knockdown of NT-3 expression and incubation with a TrkC-specific blocking antibody triggered apoptosis in human NB cell lines. Importantly, disruption of the NT-3 autocrine loop in malignant human neuroblasts triggered in vitro NB cell death and inhibited tumor growth and metastasis in both a chick and a mouse xenograft model. Thus, we believe that our data suggest that NT-3/TrkC disruption is a putative alternative targeted therapeutic strategy for the treatment of NB.

SUBMITTER: Bouzas-Rodriguez J 

PROVIDER: S-EPMC2827960 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC1948910 | biostudies-literature
| S-EPMC4040669 | biostudies-other
| S-EPMC5613966 | biostudies-literature
| S-EPMC8034437 | biostudies-literature
| S-EPMC7229216 | biostudies-literature
| S-EPMC3866601 | biostudies-literature
| S-EPMC5965893 | biostudies-literature
| S-EPMC1369188 | biostudies-literature
| S-EPMC1925242 | biostudies-other
| S-EPMC5981270 | biostudies-literature