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Título: | NAD pool as an antitumor target against cancer stem cells in head and neck cancer |
Autor: | Navas, Lola E. CSIC; Blanco-Alcaina, Elena CSIC ORCID; Suarez-Martinez, Elisa CSIC; Verdugo-Sivianes, Eva M. CSIC ORCID; Espinosa-Sánchez, Asunción CSIC; Sánchez-Díaz, Laura CSIC; Domínguez-Medina, Eduardo; Fernández-Rozadilla, Ceres; Carracedo, Ángel; Wu, Lindsay E.; Carnero, Amancio CSIC ORCID | Fecha de publicación: | 3-mar-2023 | Editor: | BioMed Central Springer Nature |
Citación: | Journal of Experimental & Clinical Cancer Research 42: 55 (2023) | Resumen: | Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumors that affect different anatomical locations. Despite this heterogeneity, HNSCC treatment depends on the anatomical location, TNM stage and resectability of the tumor. Classical chemotherapy is based on platinum-derived drugs (cisplatin, carboplatin and oxaliplatin), taxanes (docetaxel, paclitaxel) and 5-fluorouracil1. Despite advances in HNSCC treatment, the rate of tumor recurrence and patient mortality remain high. Therefore, the search for new prognostic identifiers and treatments targeting therapy-resistant tumor cells is vital. Our work demonstrates that there are different subgroups with high phenotypic plasticity within the CSC population in HNSCC. CD10, CD184, and CD166 may identify some of these CSC subpopulations with NAMPT as a common metabolic gene for the resilient cells of these subpopulations. We observed that NAMPT reduction causes a decrease in tumorigenic and stemness properties, migration capacity and CSC phenotype through NAD pool depletion. However, NAMPT-inhibited cells can acquire resistance by activating the NAPRT enzyme of the Preiss-Handler pathway. We observed that coadministration of the NAMPT inhibitor with the NAPRT inhibitor cooperated inhibiting tumor growth. The use of an NAPRT inhibitor as an adjuvant improved NAMPT inhibitor efficacy and reduced the dose and toxicity of these inhibitors. Therefore, it seems that the reduction in the NAD pool could have efficacy in tumor therapy. This was confirmed by in vitro assays supplying the cells with products of inhibited enzymes (NA, NMN or NAD) and restoring their tumorigenic and stemness properties. In conclusion, the coinhibition of NAMPT and NAPRT improved the efficacy of antitumor treatment, indicating that the reduction in the NAD pool is important to prevent tumor growth. | Descripción: | © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. | Versión del editor: | https://doi.org/10.1186/s13046-023-02631-2 | URI: | http://hdl.handle.net/10261/351981 | DOI: | 10.1186/s13046-023-02631-2 | ISSN: | 1756-9966 |
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NAD-pool_JECCR_2023_OA.pdf | 8,13 MB | Adobe PDF | Visualizar/Abrir |
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