Nutrient availability shapes methionine metabolism in p16/MTAP-deleted cells.

ABSTRACT: Codeletions of gene loci containing tumor suppressors and neighboring metabolic enzymes present an attractive synthetic dependency in cancers. However, the impact that these genetic events have on metabolic processes, which are also dependent on nutrient availability and other environmental factors, is unknown. As a proof of concept, we considered panels of cancer cells with homozygous codeletions in CDKN2a and MTAP, genes respectively encoding the commonly-deleted tumor suppressor p16 and an enzyme involved in methionine metabolism. A comparative metabolomics analysis revealed that while a metabolic signature of MTAP deletion is apparent, it is not preserved upon restriction of nutrients related to methionine metabolism. Furthermore, re-expression of MTAP exert

SUBMITTER: Sanderson SM 

PROVIDER: S-EPMC6594760 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature