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Methylthioadenosine phosphorylase deficiency in tumors: A compelling therapeutic target

The methionine salvage pathway is responsible for recycling sulfur-containing metabolites to methionine. This salvage pathway has been found to be implicated in cell apoptosis, proliferation, differentiation and inflammatory response. Methylthioadenosine phosphorylase (MTAP) catalyzes the reversible...

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Autores principales: Fan, Na, Zhang, Yi, Zou, Suyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10113547/
https://www.ncbi.nlm.nih.gov/pubmed/37091983
http://dx.doi.org/10.3389/fcell.2023.1173356
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author Fan, Na
Zhang, Yi
Zou, Suyun
author_facet Fan, Na
Zhang, Yi
Zou, Suyun
author_sort Fan, Na
collection PubMed
description The methionine salvage pathway is responsible for recycling sulfur-containing metabolites to methionine. This salvage pathway has been found to be implicated in cell apoptosis, proliferation, differentiation and inflammatory response. Methylthioadenosine phosphorylase (MTAP) catalyzes the reversible phosphorolysis of 5′-methylthioadenosine, a by-product produced from polyamine biosynthesis. The MTAP gene is located adjacent to the cyclin-dependent kinase inhibitor 2A gene and co-deletes with CDKN2A in nearly 15% of tumors. Moreover, MTAP-deleted tumor cells exhibit greater sensitivity to methionine depletion and to the inhibitors of purine synthesis. In this review, we first summarized the molecular structure and expression of MTAP in tumors. Furthermore, we discussed PRMT5 and MAT2A as a potential vulnerability for MTAP-deleted tumors. The complex and dynamic role of MTAP in diverse malignancies has also been discussed. Finally, we demonstrated the implications for the treatment of MTAP-deleted tumors.
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spelling pubmed-101135472023-04-20 Methylthioadenosine phosphorylase deficiency in tumors: A compelling therapeutic target Fan, Na Zhang, Yi Zou, Suyun Front Cell Dev Biol Cell and Developmental Biology The methionine salvage pathway is responsible for recycling sulfur-containing metabolites to methionine. This salvage pathway has been found to be implicated in cell apoptosis, proliferation, differentiation and inflammatory response. Methylthioadenosine phosphorylase (MTAP) catalyzes the reversible phosphorolysis of 5′-methylthioadenosine, a by-product produced from polyamine biosynthesis. The MTAP gene is located adjacent to the cyclin-dependent kinase inhibitor 2A gene and co-deletes with CDKN2A in nearly 15% of tumors. Moreover, MTAP-deleted tumor cells exhibit greater sensitivity to methionine depletion and to the inhibitors of purine synthesis. In this review, we first summarized the molecular structure and expression of MTAP in tumors. Furthermore, we discussed PRMT5 and MAT2A as a potential vulnerability for MTAP-deleted tumors. The complex and dynamic role of MTAP in diverse malignancies has also been discussed. Finally, we demonstrated the implications for the treatment of MTAP-deleted tumors. Frontiers Media S.A. 2023-04-05 /pmc/articles/PMC10113547/ /pubmed/37091983 http://dx.doi.org/10.3389/fcell.2023.1173356 Text en Copyright © 2023 Fan, Zhang and Zou. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Fan, Na
Zhang, Yi
Zou, Suyun
Methylthioadenosine phosphorylase deficiency in tumors: A compelling therapeutic target
title Methylthioadenosine phosphorylase deficiency in tumors: A compelling therapeutic target
title_full Methylthioadenosine phosphorylase deficiency in tumors: A compelling therapeutic target
title_fullStr Methylthioadenosine phosphorylase deficiency in tumors: A compelling therapeutic target
title_full_unstemmed Methylthioadenosine phosphorylase deficiency in tumors: A compelling therapeutic target
title_short Methylthioadenosine phosphorylase deficiency in tumors: A compelling therapeutic target
title_sort methylthioadenosine phosphorylase deficiency in tumors: a compelling therapeutic target
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10113547/
https://www.ncbi.nlm.nih.gov/pubmed/37091983
http://dx.doi.org/10.3389/fcell.2023.1173356
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