Nicotinic acid inhibits glioma invasion by facilitating Snail1 degradation
Date
2017-03-03
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Nature Publishing Group
Abstract
Malignant glioma is a formidable disease that commonly leads to death, mainly due to the invasion
of tumor cells into neighboring tissues. Therefore, inhibition of tumor cell invasion may provide an
effective therapy for malignant glioma. Here we report that nicotinic acid (NA), an essential vitamin,
inhibits glioma cell invasion in vitro and in vivo. Treatment of the U251 glioma cells with NA in vitro
results in reduced invasion, which is accompanied by a loss of mesenchymal phenotype and an increase
in cell-cell adhesion. At the molecular level, transcription of the adherens junction protein E-cadherin
is upregulated, leading to accumulation of E-cadherin protein at the cell-cell boundary. This can be
attributed to NA’s ability to facilitate the ubiquitination and degradation of Snail1, a transcription
factor that represses E-cadherin expression. Similarly, NA transiently inhibits neural crest migration in
Xenopus embryos in a Snail1-dependent manner, indicating that the mechanism of action for NA in cell
migration is evolutionarily conserved. We further show that NA injection blocks the infiltration of tumor
cells into the adjacent brain tissues and improves animal survival in a rat model of glioma. These results
suggest that NA treatment may be developed into a potential therapy for malignant glioma.
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Citation
Li, J. et al. Nicotinic acid inhibits glioma invasion by facilitating Snail1 degradation. Sci. Rep. 7, 43173; doi: 10.1038/srep43173 (2017).