Dataset Information

Impaired AKT signaling and lung tumorigenesis by PIERCE1 ablation in KRAS-mutant non-small cell lung cancer

ABSTRACT: KRAS-mutant non-small cell lung cancer (NSCLC) is one of the main subtypes across lung cancers. Despite the enormous studies on KRAS-mutant NSCLC, new therapeutic targets need to be identified because current therapies are insufficient. Here we show the tumor promoting function of PIERCE1 in the KRAS-mutant NSCLC. Mechanistically, PIERCE1 depletion inhibits cell growth and AKT phosphorylation (pAKT) at S473, particularly in KRAS-mutant lung cancer. Analyses of AKT-related genes show that PIERCE1 negatively regulates gene expression of AKT suppressor TRIB3 through CHOP pathway. Correspondingly, four independent in vivo approaches in lung cancer mouse models related to KRAS mutations reveal the tumor suppressive effect of PIERCE1 depletion suggesting its therapeutic potential. Tissue microarray of human lung cancer showed that PIERCE1 is expressed in 83% of lung cancers and is linked to pAKT expression. This illustrates how PIERCE1 depletion acts as a novel therapeutics against KRAS-mutant NSCLC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE136131 | GEO | 2020/11/02

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:Non-small cell lung cancer (NSCLC) cell lines are widely used model systems to study molecular aspects of lung cancer. Comparative and in-depth proteome expression data across many NSCLC cell lines has not been generated yet, but would be of utility for the investigation of candidate targets and markers in oncogenesis. We employed a SILAC reference approach to perform replicate proteome quantifications across 23 distinct NSCLC cell lines. On average, close to 4000 distinct proteins were identified and quantified per cell line. These included many known targets and diagnostic markers, indicating that our proteome expression data represents a useful resource for NSCLC pre-clinical research. To assess proteome diversity within the NSCLC cell line panel, we performed hierarchical clustering and principal component analysis of proteome expression data. Our results indicate that general proteome diversity among NSCLC cell lines supersedes potential effects common to K-Ras or epidermal growth factor receptor (EGFR) oncoprotein expression. However, we observed partial segregation of EGFR or KRAS mutant cell lines for certain principal components, which reflected biological differences according to gene ontology enrichment analyses. Moreover, statistical analysis revealed several proteins that were significantly overexpressed in KRAS or EGFR mutant cell lines. Biological significance Despite enormous progress in molecular characterization and targeted therapy NSCLC represents a major cause for cancer-related deaths. While pre-clinical models such as NSCLC cell lines have been studied on the genomic and transcriptional level, proteome composition is poorly characterized. We conducted quantitative profiling across 23 NSCLC cell lines and studied global proteome diversity in relation to the presence of oncogenic KRAS or EGFR mutations. Notably, in-depth bioinformatics analysis pointed to prominent biological processes as well as up-regulated proteins in KRAS and EGFR mutant cells, highlighting the utility of cancer cell proteomics to identify target or biomarker candidates in the context of specific oncogenic mechanisms.

Dataset Information

Impaired AKT signaling and lung tumorigenesis by PIERCE1 ablation in KRAS-mutant non-small cell lung cancer

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure