Nutrient availability shapes methionine metabolism in p16/MTAP-deleted cells.
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 exerts heterogeneous consequences on metabolism across isogenic cell pairs. Together, this study demonstrates that numerous factors, particularly nutrition, can overwhelm the effects of metabolic gene deletions on metabolism. These findings may also have relevance to drug development efforts aiming to target methionine metabolism.
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- Sequence Deletion
- Nutrients
- Neoplasms
- Methionine
- Humans
- Cyclin-Dependent Kinase Inhibitor p16
- Cell Line, Tumor
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Sequence Deletion
- Nutrients
- Neoplasms
- Methionine
- Humans
- Cyclin-Dependent Kinase Inhibitor p16
- Cell Line, Tumor