A05
Contribution of the ubiquitin proteasome system to ferroptosis resistance in non-small cell lung cancers
Project Summary
Mutations in the KEAP1 E3 ligase are identified in 30% of patients with NSCLC. These mutations trigger abnormal activation of NRF2, a factor linked to resistance to cell death and therapies. Using a CRISPR screen in KEAP1-mutant and non-mutant cells, we found a relationship between cell death caused by the ferroptosis inducer FIN56 and the CRL5 ubiquitylation system. Here, we plan to characterize CRL5 substrates and modulators that contribute to FIN56-induced cell death and to explore their contribution to NSCLC growth. These will reveal the cause of ferroptosis resistance in NSCLC and provide the basis for developing innovative combination strategies to combat this disease.
