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 Jimenez-Garcia, Manuel P.
A1 Peinado-Serrano, Javier
A1 Carnero, Amancio
K1 NAMPT
K1 cancer initiating cell
K1 gene signature
K1 glioma
K1 glioblastoma
K1 Nicotinamide phosphoribosyltransferase
K1 Heterogeneity implications
K1 Glioblastoma-multiforme
K1 Anaplastic glioma
K1 Target therapies
K1 Cell-death
K1 Metabolism
K1 Biology
K1 Nad(+)
K1 Subtypes
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.
PB Impact journals llc
YR 2017
FD 2017-11-21
LK http://hdl.handle.net/10668/19442
UL http://hdl.handle.net/10668/19442
LA en
DS RISalud
RD Apr 4, 2025