Project description:BCL11A is upregulated in lung squamous cell carcinoma (LUSC) but not in lung adenocarcinoma (LUAD). BCL11A interacts with SOX2 at protein level. ChIP-Seq experiment was performed for BCL11A and SOX2 in LUSC LK-2 control or BCL11A-KD cell line in order to identify their role in LUSC pathology.
Project description:Lung cancer in Chinese patients has distinct genomic features and lung squamous cell carcinoma (LUSC) has limited biomarkers for targeted therapy even though a lot of progress has been made in genomics research. Systematical research on LUSC at protein level will be beneficial to improve precision medicine. In this study, the large scale proteomics and phosphoproteomics analysis on clinical Chinese LUSC patients were performed.
2020-05-16 | PXD019234 |
Project description:Lung squamous cell carcinoma (LUSC) long read genomic analysis
Project description:Non-small cell lung cancer (NSCLC) comprises the majority (~85%) of all lung tumors, with lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) being the most frequently diagnosed histological subtypes. Currently, multi-modal omics profiles had been carried out in NSCLC, but no studies reported yet a systems biology approach to provide a complete picture of molecular perturbations specifically for LUAD and LUSC.
Project description:Lung squamous cell carcinoma (LUSC) is associated with high mortality and limited targeted therapies. USP13 is one of the most amplified genes in LUSC, and yet its role in lung cancer is largely unknown. Here, we establish a novel mouse model of LUSC by overexpressing USP13 in KrasG12D/+; Trp53flox/flox background (KPU). KPU model faithfully recapitulates the key pathohistological, molecular features, and cellular pathways of human LUSC. We found that USP13 altered lineage-determining factors such as NKX2-1 and SOX2 in club cells (CC10+) of the airway and reinforced the fate of club cells to squamous carcinoma development. We also showed a strong molecular association between USP13 and MYC, leading to the upregulation of squamous programs in murine and human lung cancer cells. Collectively, our data demonstrate USP13 as a molecular driver of lineage plasticity in club cells and provide mechanistic insight that may have potential implications for the treatment of NSCLC.
Project description:Lung cancer is the leading cause of cancer mortality due to limited diagnosis and interception of disease at its earliest curable stages. We have identified transcriptional alterations in epithelial and immune pathways in human lung squamous premalignant lesions (PMLs). To investigate the molecular alterations identified and test prevention strategies pre-clinical models are required. The carcinogen induced N-nitroso-tris-chloroethylurea (NTCU) mouse model of lung squamous cell carcinoma (LUSC) is a promising model that develops histologically comparable lung PMLs to those that precede LUSC development in humans; however, the associated molecular alterations and immune environment driving PML and LUSC development in this model have not been well characterized.
Project description:To investigate the subcellular localization of maspin in lung squamous cell carcinoma (LUSC) and its functional relevance, gene expression profiles were analyzed in RERF-LC-AI and LK-2 cells overexpressing maspin. The data provides insight into the differential function of maspin in LUSC depending on its subcellular localization.
Project description:Lineage-specific transcriptional regulators control differentiation states not only during normal development but also during cancer evolution. By investigating super-enhancer landscape of lung squamous cell carcinoma (LUSC), we identified a unique ‘neural’ subtype defined by Sox2 and a neural lineage factor Brn2. Robust protein-protein interaction and genomic co-occupancy of these factors indicated their transcriptional cooperation in this ‘neural’ LUSC in contrast to the cooperation of Sox2 and p63 in the classical LUSC. Introduction of p63 expression in the “neural’ LUSC invoked the classical LUSC lineage accompanied by Brn2 downregulation and increased activities of ErbB/Akt and MAPK-ERK pathways. Collectively, our data demonstrate a unique LUSC lineage featured by Sox2 cooperation with Brn2 instead of p63, for which distinct therapeutic approaches may be warranted.
