Molecular insights into SMARCA2 degradation in SMARCA4-mutant lung cancers

Abstract

The molecular mechanisms of switch/sucrose nonfermentable (SWI/SNF)-related BAF chromatin remodeling complex subunit ATPase 2 (SMARCA2) degradation remain elusive. Recently, Kotagiri et al. revealed that SMARCA2 degradation induces enhancer reprogramming in SMARCA4-mutant lung cancer cells, rendering enhancers of key cell-cycle genes inaccessible and suppressing their expression. In addition, the authors identified that transcriptional enhanced associate domain (TEAD) inhibitors synergize with SMARCA2 degraders in inhibiting SMARCA4-mutant lung cancer growth.

Keywords: SMARCA2 degrader; SMARCA4-mutant cancers; TEAD inhibitor; chromatin accessibility; enhancer reprogramming; lung cancer.