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Nicotinamide N-Methyltransferase as Promising Tool for Management of Gastrointestinal Neoplasms

Gastrointestinal (GI) neoplasms include esophageal, gastric, colorectal, hepatic, and pancreatic cancers. They are characterized by asymptomatic behavior, being responsible for diagnostic delay. Substantial refractoriness to chemo- and radiotherapy, exhibited by late-stage tumors, contribute to dete...

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Autores principales: Pozzi, Valentina, Campagna, Roberto, Sartini, Davide, Emanuelli, Monica
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496617/
https://www.ncbi.nlm.nih.gov/pubmed/36139012
http://dx.doi.org/10.3390/biom12091173
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author Pozzi, Valentina
Campagna, Roberto
Sartini, Davide
Emanuelli, Monica
author_facet Pozzi, Valentina
Campagna, Roberto
Sartini, Davide
Emanuelli, Monica
author_sort Pozzi, Valentina
collection PubMed
description Gastrointestinal (GI) neoplasms include esophageal, gastric, colorectal, hepatic, and pancreatic cancers. They are characterized by asymptomatic behavior, being responsible for diagnostic delay. Substantial refractoriness to chemo- and radiotherapy, exhibited by late-stage tumors, contribute to determine poor patient outcome. Therefore, it is of outmost importance to identify new molecular targets for the development of effective therapeutic strategies. In this study, we focused on the enzyme nicotinamide N-methyltransferase (NNMT), which catalyzes the N-methylation reaction of nicotinamide and whose overexpression has been reported in numerous neoplasms, including GI cancers. The aim of this review was to report data illustrating NNMT involvement in these tumors, highlighting its contribution to tumor cell phenotype. Cited works clearly demonstrate the interesting potential use of enzyme level determination for both diagnostic and prognostic purposes. NNMT was also found to positively affect cell viability, proliferation, migration, and invasiveness, contributing to sustain in vitro and in vivo tumor growth and metastatic spread. Moreover, enzyme upregulation featuring tumor cells was significantly associated with enhancement of resistance to treatment with chemotherapeutic drugs. Taken together, these results strongly suggest the possibility to target NNMT for setup of molecular-based strategies to effectively treat GI cancers.
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spelling pubmed-94966172022-09-23 Nicotinamide N-Methyltransferase as Promising Tool for Management of Gastrointestinal Neoplasms Pozzi, Valentina Campagna, Roberto Sartini, Davide Emanuelli, Monica Biomolecules Review Gastrointestinal (GI) neoplasms include esophageal, gastric, colorectal, hepatic, and pancreatic cancers. They are characterized by asymptomatic behavior, being responsible for diagnostic delay. Substantial refractoriness to chemo- and radiotherapy, exhibited by late-stage tumors, contribute to determine poor patient outcome. Therefore, it is of outmost importance to identify new molecular targets for the development of effective therapeutic strategies. In this study, we focused on the enzyme nicotinamide N-methyltransferase (NNMT), which catalyzes the N-methylation reaction of nicotinamide and whose overexpression has been reported in numerous neoplasms, including GI cancers. The aim of this review was to report data illustrating NNMT involvement in these tumors, highlighting its contribution to tumor cell phenotype. Cited works clearly demonstrate the interesting potential use of enzyme level determination for both diagnostic and prognostic purposes. NNMT was also found to positively affect cell viability, proliferation, migration, and invasiveness, contributing to sustain in vitro and in vivo tumor growth and metastatic spread. Moreover, enzyme upregulation featuring tumor cells was significantly associated with enhancement of resistance to treatment with chemotherapeutic drugs. Taken together, these results strongly suggest the possibility to target NNMT for setup of molecular-based strategies to effectively treat GI cancers. MDPI 2022-08-24 /pmc/articles/PMC9496617/ /pubmed/36139012 http://dx.doi.org/10.3390/biom12091173 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Pozzi, Valentina
Campagna, Roberto
Sartini, Davide
Emanuelli, Monica
Nicotinamide N-Methyltransferase as Promising Tool for Management of Gastrointestinal Neoplasms
title Nicotinamide N-Methyltransferase as Promising Tool for Management of Gastrointestinal Neoplasms
title_full Nicotinamide N-Methyltransferase as Promising Tool for Management of Gastrointestinal Neoplasms
title_fullStr Nicotinamide N-Methyltransferase as Promising Tool for Management of Gastrointestinal Neoplasms
title_full_unstemmed Nicotinamide N-Methyltransferase as Promising Tool for Management of Gastrointestinal Neoplasms
title_short Nicotinamide N-Methyltransferase as Promising Tool for Management of Gastrointestinal Neoplasms
title_sort nicotinamide n-methyltransferase as promising tool for management of gastrointestinal neoplasms
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496617/
https://www.ncbi.nlm.nih.gov/pubmed/36139012
http://dx.doi.org/10.3390/biom12091173
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