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NAMPT overexpression induces cancer stemness and defines a novel tumor signature for glioma prognosis

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 tissu...

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Autores principales: Lucena-Cacace, Antonio, Otero-Albiol, Daniel, Jiménez-García, Manuel P., Peinado-Serrano, Javier, Carnero, Amancio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725111/
https://www.ncbi.nlm.nih.gov/pubmed/29245920
http://dx.doi.org/10.18632/oncotarget.20577
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author Lucena-Cacace, Antonio
Otero-Albiol, Daniel
Jiménez-García, Manuel P.
Peinado-Serrano, Javier
Carnero, Amancio
author_facet Lucena-Cacace, Antonio
Otero-Albiol, Daniel
Jiménez-García, Manuel P.
Peinado-Serrano, Javier
Carnero, Amancio
author_sort Lucena-Cacace, Antonio
collection PubMed
description 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.
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spelling pubmed-57251112017-12-14 NAMPT overexpression induces cancer stemness and defines a novel tumor signature for glioma prognosis Lucena-Cacace, Antonio Otero-Albiol, Daniel Jiménez-García, Manuel P. Peinado-Serrano, Javier Carnero, Amancio Oncotarget Research Paper 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. Impact Journals LLC 2017-08-28 /pmc/articles/PMC5725111/ /pubmed/29245920 http://dx.doi.org/10.18632/oncotarget.20577 Text en Copyright: © 2017 Lucena-Cacace et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Lucena-Cacace, Antonio
Otero-Albiol, Daniel
Jiménez-García, Manuel P.
Peinado-Serrano, Javier
Carnero, Amancio
NAMPT overexpression induces cancer stemness and defines a novel tumor signature for glioma prognosis
title NAMPT overexpression induces cancer stemness and defines a novel tumor signature for glioma prognosis
title_full NAMPT overexpression induces cancer stemness and defines a novel tumor signature for glioma prognosis
title_fullStr NAMPT overexpression induces cancer stemness and defines a novel tumor signature for glioma prognosis
title_full_unstemmed NAMPT overexpression induces cancer stemness and defines a novel tumor signature for glioma prognosis
title_short NAMPT overexpression induces cancer stemness and defines a novel tumor signature for glioma prognosis
title_sort nampt overexpression induces cancer stemness and defines a novel tumor signature for glioma prognosis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725111/
https://www.ncbi.nlm.nih.gov/pubmed/29245920
http://dx.doi.org/10.18632/oncotarget.20577
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