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Published on: February 6, 2015
Proteomic Analysis of the Non-genetic Response to Cisplatin in Lung Cancer Cells
Cristine DE Souza Dutra1, Carolina Lumertz Martello1, Nathan Araujo Cadore1
1Laboratório de Genômica Estrutural e Funcional, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Background:
Drug resistance is the main cause of therapy failure in advanced lung cancer. Although non-genetic mechanisms play important roles in tumor chemoresistance, drug-induced epigenetic reprogramming is still poorly understood.
Materials And Methods:
The A549 cell line was used to generate cells with non-genetic resistance to cisplatin (CDDP), namely A549/CDDP cells. Bioorthogonal non-canonical amino acid tagging (BONCAT) and mass spectrometry were used to identify proteins modulated by CDDP in A549 and A549/CDDP cells.
Results:
Proteins related to proteostasis, telomere maintenance, cell adhesion, cytoskeletal remodeling, and cell redox homeostasis were found enriched in both cell lines upon CDDP exposure. On the other hand, proteins involved in drug response, metabolic pathways and mRNA processing and splicing were up-regulated by CDDP only in A549/CDDP cells.
Conclusion:
Our study revealed proteome dynamics involved in the non-genetic response to CDDP, pointing out potential targets to monitor and overcome epigenetic resistance in lung cancer.
Insights
Drug resistance in lung cancer is poorly understood. This study reveals proteome changes in cisplatin-resistant lung cancer cells, identifying potential targets to overcome chemoresistance.
Area of Science:
- Proteomics
- Cancer Biology
- Epigenetics
Background:
- Drug resistance is a major cause of treatment failure in advanced lung cancer.
- Non-genetic mechanisms contribute significantly to chemoresistance, but drug-induced epigenetic reprogramming remains unclear.
Purpose of the Study:
- To investigate the proteomic changes associated with non-genetic cisplatin resistance in lung cancer.
- To identify potential molecular targets for overcoming epigenetic resistance.
Main Methods:
- Generated cisplatin-resistant A549/CDDP lung cancer cells.
- Utilized bioorthogonal non-canonical amino acid tagging (BONCAT) and mass spectrometry to analyze protein expression.
- Compared proteomes of sensitive (A549) and resistant (A549/CDDP) cells upon cisplatin exposure.
Main Results:
- Proteins involved in proteostasis, telomere maintenance, cell adhesion, cytoskeletal remodeling, and redox homeostasis were modulated by cisplatin in both cell lines.
- Cisplatin specifically upregulated proteins related to drug response, metabolic pathways, and mRNA processing/splicing in resistant cells.
- Revealed distinct proteome dynamics underlying non-genetic cisplatin resistance.
Conclusions:
- The study elucidates proteome dynamics in the non-genetic response to cisplatin.
- Identified potential targets for monitoring and overcoming epigenetic resistance in lung cancer therapy.
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