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Quantitative Mass Spectrometric Profiling of Cancer-cell Proteomes Derived From Liquid and Solid Tumors
Published on: February 27, 2015
Proteome and phosphoproteome profiling of non-small cell lung cancer cell line A549 treated with TRAIL
1Proteomics-Metabolomics Platform of Core Facilities, Key Lab of Transplant Engineering and Immunology, MOH, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
Abstract:
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is recognized for its promising therapeutic effects against cancer. However, mechanisms underlying the effect of TRAIL on protein expression, signal transduction, and apoptosis induction remain unclear. We surmised that a systematic analysis of the proteome and phosphoproteome associated with TRAIL signaling may help elucidate the mechanisms involved and facilitate the development of therapeutics. Therefore, we investigated the proteome and phosphoproteome of non-small cell lung cancer cell line A549 treated with TRAIL. Our results indicated that 126 proteins and 1684 phosphosites were markedly differentially expressed between the phosphate-buffered saline- and TRAIL-treated groups. The expression at protein and phosphosite levels were not completely consistent. Gene ontology functional analysis revealed that metal ion (zinc) binding was highly affected by TRAIL treatment. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that almost all pathways that involved differentially expressed phosphosites were associated with apoptosis. We also identified an important kinase, AKT1, and its series of substrates in TRAIL signaling. The results of this study may provide guidance for future research on tumor therapy using TRAIL.
Insights
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) treatment significantly alters protein and phosphosite expression in lung cancer cells. This proteomic and phosphoproteomic analysis reveals key pathways involved in apoptosis and identifies AKT1 as a crucial kinase in TRAIL signaling.
Area of Science:
- Proteomics and phosphoproteomics
- Cancer biology
- Molecular signaling pathways
Background:
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) shows therapeutic potential against cancer.
- The precise mechanisms of TRAIL's action on protein expression, signal transduction, and apoptosis remain incompletely understood.
Purpose of the Study:
- To systematically analyze the proteome and phosphoproteome in response to TRAIL signaling in non-small cell lung cancer (NSCLC).
- To elucidate the molecular mechanisms underlying TRAIL-induced apoptosis and identify potential therapeutic targets.
Main Methods:
- Proteomic and phosphoproteomic profiling of A549 NSCLC cells treated with TRAIL.
- Differential expression analysis of proteins and phosphosites.
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses.
- Identification of key kinases and their substrates in TRAIL signaling.
Main Results:
- Significant differential expression of 126 proteins and 1684 phosphosites upon TRAIL treatment.
- Inconsistent expression patterns observed between protein and phosphosite levels.
- TRAIL treatment notably impacts metal ion (zinc) binding.
- Apoptosis-related pathways were predominantly enriched among differentially expressed phosphosites.
- The kinase AKT1 and its substrates were identified as key players in TRAIL signaling.
Conclusions:
- Proteomic and phosphoproteomic analyses provide insights into TRAIL signaling mechanisms in NSCLC.
- The findings highlight the role of AKT1 and zinc binding in TRAIL-mediated apoptosis.
- This study offers guidance for developing TRAIL-based cancer therapeutics.
