MassIVE MSV000097246

Partial Public PXD061550

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

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Description

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) [doi:10.25345/C5HH6CJ48] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: KRAS, STK11/LKB1, MCL-1, non-small cell lung cancer, apoptosis, Phosphoproteomics, Orbitrap Fusion Lumos, TMT ; DatasetType:Proteomics

Contact

Principal Investigators:
(in alphabetical order) 		Aaron N Hata, Massachusetts General Hospital and Harvard Medical School, United States
Chendi Li, Massachusetts General Hospital and Harvard Medical School, United States
Wilhelm Haas, Massachusetts General Hospital and Harvard Medical School, United States
Submitting User: jkreuzer

Publications

Li C, Syed MU, Nimbalkar A, Shen Y, Vieira MD, Fraser C, Inde Z, Qin X, Ouyang J, Kreuzer J, Clark SE, Kelley G, Hensley EM, Morris R, Lazaro R, Belmonte B, Oh A, Walcott M, Nabel CS, Caenepeel S, Saiki AY, Rex K, Lipford JR, Heist RS, Lin JJ, Haas W, Sarosiek K, Hughes PE, Hata AN.
LKB1 regulates JNK-dependent stress signaling and apoptotic dependency of KRAS-mutant lung cancers.
Nat Commun. 2025 May 2;16(1):4112. Epub 2025 May 2.

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