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Updated: Jul 26, 2025
Quantitative Mass Spectrometric Profiling of Cancer-cell Proteomes Derived From Liquid and Solid Tumors
Published on: February 27, 2015
Proteomic Dynamics of Breast Cancer Cell Lines Identifies Potential Therapeutic Protein Targets
Rui Sun1, Weigang Ge2, Yi Zhu3
1Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China.
Abstract:
Treatment and relevant targets for breast cancer (BC) remain limited, especially for triple-negative BC (TNBC). We identified 6091 proteins of 76 human BC cell lines using data-independent acquisition (DIA). Integrating our proteomic findings with prior multi-omics datasets, we found that including proteomics data improved drug sensitivity predictions and provided insights into the mechanisms of action. We subsequently profiled the proteomic changes in nine cell lines (five TNBC and four non-TNBC) treated with EGFR/AKT/mTOR inhibitors. In TNBC, metabolism pathways were dysregulated after EGFR/mTOR inhibitor treatment, while RNA modification and cell cycle pathways were affected by AKT inhibitor. This systematic multi-omics and in-depth analysis of the proteome of BC cells can help prioritize potential therapeutic targets and provide insights into adaptive resistance in TNBC.
Insights
This study analyzed breast cancer (BC) cell proteins to improve drug sensitivity predictions, especially for triple-negative breast cancer (TNBC). Proteomics data revealed key pathway changes in TNBC cells treated with targeted inhibitors.
Area of Science:
- Oncology
- Proteomics
- Genomics
Background:
- Targeted therapies for breast cancer (BC), particularly triple-negative breast cancer (TNBC), are limited.
- Understanding the proteomic landscape is crucial for identifying new therapeutic strategies.
Purpose of the Study:
- To identify potential therapeutic targets for breast cancer by analyzing proteomic data.
- To investigate the effects of EGFR/AKT/mTOR inhibitors on proteomic changes in BC and TNBC cell lines.
- To improve drug sensitivity predictions by integrating multi-omics datasets.
Main Methods:
- Proteomic profiling of 76 human BC cell lines using data-independent acquisition (DIA).
- Integration of proteomic findings with existing multi-omics datasets.
- Analysis of proteomic alterations in nine BC cell lines (five TNBC, four non-TNBC) upon treatment with EGFR/AKT/mTOR inhibitors.
Main Results:
- Proteomics data integration enhanced drug sensitivity predictions and elucidated mechanisms of action.
- In TNBC cells, EGFR/mTOR inhibition dysregulated metabolism pathways.
- AKT inhibition affected RNA modification and cell cycle pathways in TNBC cells.
Conclusions:
- Systematic multi-omics analysis of BC cell proteomes aids in prioritizing therapeutic targets.
- In-depth proteomic insights can illuminate adaptive resistance mechanisms in TNBC.
- This approach offers a foundation for developing more effective BC treatments.
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