NAMPT as a Dedifferentiation-Inducer Gene: NAD+ as Core Axis for Glioma Cancer Stem-Like Cells Maintenance

Conclusion and Perspectives Gliomas are the most prevalent primary brain cancer in adults and include a broad category of tumors including astrocytoma, oligodendroglioma, and GBM. Regardless of tumor aggressiveness, malignancy, and infiltration, these glia-derived tumors rarely exceed a median survival time of 12–14 months. Driven by the infiltrative nature of these tumors, the clinical approach is difficult and relapses often occur with fatal consequences. These unsuccessful attempts to control glioma's fate have fostered research looking for more effective therapies. (GSCs) are a small subset of CD133+ cells with self-renewal properties and capable of initiating new tumors contributing to Glioma progression, maintenance, hierarchy and complexity. GSCs are highly resistant to chemo and radiotherapy. These cells are believed to be responsible for tumor relapses and patients' fatal outcome after developing a recurrent GBM or High Grade Glioma (HGG). GSCs are cells under replicative stress with high demands on NAD+ supply to repair DNA, maintain self-renewal capacity and to induce tumor plasticity. NAD+ feeds Poly-ADP polymerases (PARP) and NAD+-dependent deacetylases (SIRTUINS) contributing to GSC phenotype. Ablation of NAMPT showed to impair Schwann cell differentiation program associated to reduced NAD+ levels, counteracting the phenotype found in tumor cells but reinforcing the idea that an adequate NAD�...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research