2026/03/17 by Mohammed Bourouh, Jinhong Kim, Paola A. Marignani · 1 voice
Biochemistry, Genetics and Molecular Biology · #Chromatin Remodeling and Cancer #Genomics and Chromatin Dynamics #Mechanisms of cancer metastasis
paper · pdf · doi:10.3389/fcell.2026.1685342
openalex publication_date 2026/03/17 · openalex created_date 2026/03/18 · openalex updated_date 2026/07/23
Introduction: The tumor suppressor kinase liver kinase B1 (LKB1) is known to regulate the activity of the metabolic sensor AMP-activated protein kinase (AMPK), which, under energy stress, shifts metabolism from anabolism to catabolism, thus linking LKB1 to AMPK-mediated gene expression. Coupled with its role as a tumor suppressor kinase, LKB1 is an important metabolic regulator implicated in multiple malignancies and is frequently mutated in lung cancer. Previously, we discovered that LKB1 binds to the switch/sucrose non-fermenting (SWI/SNF) chromatin remodeling ATP-dependent helicase subunit SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4), directly linking LKB1 to gene expression. How LKB1 and SMARCA4 collaborate to regulate gene expression in lung cancer has not been well characterized. Methods: expression status to identify genes regulated by both LKB1 and SMARCA4. We correlated our results using bulk RNA-seq results from human lung tumors. Results: We show that LKB1 and SMARCA4 likely function together to regulate gene expression in multiple biological processes in lung cancer cell lines. Gene expression profiles from LKB1- and SMARCA4-mutant cells are similar, suggesting that LKB1 and SMARCA4 function in a linear pathway to regulate gene expression. Furthermore, we observed similar results in human lung tumors, particularly in late-stage disease. Discussion: We propose a model where LKB1 acts as a nexus between metabolism and gene expression, acting via the SMARCA4-SWI/ SNF complex to regulate gene expression in lung cancer.