Transcriptional regulation by LKB1 in lung adenocarcinomas: Exploring oxidative stress, neuroglial and amino acid signatures.

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Tác giả: Jordan Allard, Sandrine Blanchet, Pierre Hainaut, Marie Mével-Aliset, Emilie Montellier, Guillermo A Orsi, Anca G Radu, Rodrigue Rossignol, Chantal Thibert, Sakina Torch

Ngôn ngữ: eng

Ký hiệu phân loại: 809.008 History and description with respect to kinds of persons

Thông tin xuất bản: United States : Biochemical and biophysical research communications , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 710941

Lung adenocarcinoma (LUAD) is one of the most prevalent cancer types worldwide and has one of the poorest survival rates. Understanding its developpment is crucial for improving diagnosis, prognosis, and treatment. A key factor in LUAD is the frequent loss-of-function mutations in LKB1/STK11, a kinase that regulates metabolism. These mutations are linked to increased metastasis and worse clinical outcomes. In this study, we analyzed gene expression data from LUAD patients to explore how LKB1 mutations affect cancer behavior. We found that LKB1 mutations in KRAS-driven LUAD lead to widespread gene downregulation. By integrating avalaible protein interaction data, mass spectrometry analysis of LKB1 nuclear partners, and co-immunoprecipitations experiments, we identified BRG1, a chromatin activator and subunit of the BAF complex, as a nuclear partner of LKB1. Further analysis suggested that LKB1 mutations may impair BRG1 activity, disrupting chromatin regulation and gene expression. Notably, LUAD patients with mutated LKB1 showed gene expression patterns indicative of oxidative stress, defective neuronal-glial and neuroinflammation programs, and altered amino acid homeostasis. These changes resemble the roles LKB1 plays in neural crest stem cells, suggesting that LKB1 may reduce tumor aggressiveness in LUAD by maintaining a developmental gene expression program.
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