RT Journal Article
T1 NAMPT overexpression induces cancer stemness and defines a novel tumor signature for glioma prognosis.
A1 Lucena-Cacace, Antonio
A1 Otero-Albiol, Daniel
A1 Jiménez-García, Manuel P
A1 Peinado-Serrano, Javier
A1 Carnero, Amancio
K1 NAMPT
K1 cancer initiating cell
K1 gene signature
K1 glioblastoma
K1 glioma
AB Gliomas are the most prevalent primary malignant brain tumors associated with poor prognosis. NAMPT, a rate-limiting enzyme that boosts the nicotinamide adenine dinucleotide (NAD) regeneration in the salvage pathway, is commonly expressed in these tumors. NAD metabolism is required to maintain tissue homeostasis. To maintain metabolism, cancer cells require a stable NAD regeneration circuit. However, high levels of NAD confer resistance to therapy to these tumors, usually treated with Temozolomide (TMZ). We report that NAMPT overexpression in glioma cell lines increases tumorigenic properties controlling stem cell pathways and enriching the cancer-initiating cell (CIC) population. Furthermore, NAMPT expression correlated with high levels of Nanog, CD133 and CIC-like cells in glioblastoma directly extracted from patients. Meta-analysis reveals that NAMPT is also a key factor inducing cancer stem pathways in glioma cells. Furthermore, we report a novel NAMPT-driven signature which stratify prognosis within tumor staging. NAMPT signature also correlates directly with EGFR positive and IDH negative tumors. Finally, NAMPT inhibition increases sensitivity to apoptosis in both NAMPT-expressing cells and tumorspheres. Therefore, NAMPT represents a novel therapeutic target in Glioma progression and relapse.
YR 2017
FD 2017-08-28
LK https://hdl.handle.net/10668/25140
UL https://hdl.handle.net/10668/25140
LA en
DS RISalud
RD Apr 8, 2025