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...

Full description

Saved in:
Bibliographic Details
Published inFrontiers in cell and developmental biology Vol. 11; p. 1173356
Main Authors Fan, Na, Zhang, Yi, Zou, Suyun
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 05.04.2023
Subjects
CDKN2A
Cell and Developmental Biology
glioma
methionine salvage pathway
MTAP
tumor
glioma
MTAP
methionine salvage pathway
CDKN2A
tumor
Online AccessGet full text

Cover

More Information
Summary: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.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-3
content type line 23
ObjectType-Review-1
Edited by: Aisha Farhana, College of Applied Medical Sciences, Saudi Arabia
Reviewed by: Ching-Hsien Chen, University of California Davis, United States
This article was submitted to Epigenomics and Epigenetics, a section of the journal Frontiers in Cell and Developmental Biology
ISSN:2296-634X
2296-634X
DOI:10.3389/fcell.2023.1173356