Excess cysteine drives conjugate formation and impairs proliferation of NRF2-activated cancer cells - PubMed
3 hours ago
- #Cancer vulnerability
- #NRF2 activation
- #Cysteine metabolism
- Cancer cells with NRF2 activation absorb more cystine than needed for standard pathways, suggesting undiscovered metabolic outcomes.
- Researchers identified known and novel cysteine-derived metabolites in NRF2-activated cancer cells, including conjugates formed with endogenous sugar metabolites.
- These cysteine-derived conjugates are present in mouse and human lung cancer samples, enriched specifically in tumors with NRF2 activation.
- NRF2 increases cystine uptake via SLC7A11 expression, elevating intracellular cysteine levels to drive these metabolic pathways across cancer cell lines.
- NRF2 activation makes cells vulnerable to high cystine environments, where excess free cysteine hampers proliferation, partly mitigated by forming conjugates.