LKB1 regulates JNK-dependent stress signaling and apoptotic dependency of KRAS-mutant lung cancers

ABSTRACT: KRAS-mutant lung cancers frequently have inactivating mutations in LKB1, which enhances tumor growth, metastasis, and immune evasion. This study shows that LKB1 suppresses JNK stress signaling, and its loss in KRAS-mutant cells leads to JNK hyperactivation and apoptotic rewiring, making them sensitive to MCL-1 inhibition. These findings highlight a previously unknown role of LKB1 in stress signaling and suggest a potential therapeutic approach for LKB1-deficient KRAS-mutant lung cancers. Multiplexed proteomics and phosphoproteomics was performed using TMT tags and the SPS3 method on an Orbitrap Fusion Lumos instrument. Sample key is as follows: H2030 EV TRAM (126), H2030 LKB1 VEH (127N), H358 sgGFP TRAM (127C), H358 sgLKB1 VEH (128N), H2030 LKB1K87I (kd) TRAM (128C), H358 sgLKB1 TRAM (129N), H358 sgGFP VEH (129C), H2030 LKB1 TRAM (130N), H2030 LKB1K87I (kd) VEH (130C), H2030 EV VEH (131N)

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Wilhelm Haas   Chendi Li   Aaron N Hata  

PROVIDER: MSV000097246 | MassIVE | Thu Mar 06 15:35:00 GMT 2025

SECONDARY ACCESSION(S): PXD061550

REPOSITORIES: MassIVE