Proteomic Dynamics of Breast Cancers Identifies Potential Therapeutic Protein Targets

Sun, R.; Zhu, Y. J.; Savad, A.; Ge, W.; Luna, A.; Liang, S.; Segura, L. T.; Rajapakse, V. N.; Yu, C.; Zhang, H.; Fang, J.; Wu, F.; Xie, H.; Saez-Rodriguez, J.; Ying, H.; Reinhold, W. C.; Sander, C.; Pommier, Y.; Neel, B. G.; Guo, T.; Aebersold, R.

doi:10.1101/2022.06.03.494776

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bioRxiv · 10.1101/2022.06.03.494776

Proteomic Dynamics of Breast Cancers Identifies Potential Therapeutic Protein Targets

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Abstract

Treatment and relevant targets for breast cancer (BC) remain limited, especially for triple-negative BC (TNBC). We quantified the proteomes of 76 human BC cell lines using data independent acquisition (DIA) based proteomics, identifying 6091 proteins. We then established a 24-protein panel distinguishing TNBC from other BC types. Integrating prior multi-omics datasets with the present proteomic results to predict the sensitivity of 90 drugs, we found that proteomics data improved drug sensitivity predictions. The sensitivity of the 90 drugs was mainly associated with cell cytoskeleton, signal transduction and mitochondrial function. We next profiled the proteome changes of nine cell lines (five TNBC cell lines, four non-TNBC cell lines) perturbated by EGFR/AKT/mTOR inhibitors. In the TNBC cell lines, metabolism pathways were dysregulated after EGFR/mTOR inhibitors treatment, while RNA modification and cell cycle pathways were dysregulated after AKT inhibitor treatment. Our study presents a systematic multi-omics and in-depth analysis of the proteome of BC cells. This work aims to aid in prioritization of potential therapeutic targets for TNBC as well as to provide insight into adaptive drug resistance in TNBC.

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Sun, R., Zhu, Y. J., Savad, A., Ge, W., Luna, A., Liang, S., Segura, L. T., Rajapakse, V. N., Yu, C., Zhang, H., Fang, J., Wu, F., Xie, H., Saez-Rodriguez, J., Ying, H., Reinhold, W. C., Sander, C., Pommier, Y., Neel, B. G., Guo, T., Aebersold, R.. 2022-06-05. Proteomic Dynamics of Breast Cancers Identifies Potential Therapeutic Protein Targets. https://doi.org/10.1101/2022.06.03.494776

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