Integrated proteome, phospho-proteome and malonyl-proteome revealed a molecular alteration of breast cancer

Breast cancer is a heterogeneous disease with a high incidence, but its proteomes have not yet been thoroughly characterized. To construct a comprehensive dynamic network of breast cancer-related proteins, we integrated the whole-cell proteome (WCP), phospho-proteome, malonyl-proteome of breast cancer tumor tissues and adjacent healthy tissues. We identified 2,417 differentially expressed proteins (DEPs), 646 differentially phosphorylated proteins (DPPs), and 107 differentially malonylated proteins (DMPs). Functional enrichment analysis revealed that these differentially expressed proteins are involved in extracellular matrix (ECM) interactions and immune-related pathways. Protein‒protein interaction (PPI) analysis revealed posttranslational modification (PTM) crosstalk between proteins involved in phosphorylation and malonylation. The acetyltransferase EP300 and deacetylase HDAC1 are involved in the DPP network, whereas the phosphatase PKM is a hub protein in the DMP network. Kinase-substrate enrichment analysis (KSEA) revealed the activation of the kinases CSNK1D, ROCK1, ROCK2, and CDK2. Overall, this study provides a foundation for understanding the functions of phosphorylation and malonylation in breast cancer. It systematically reveals critical features of breast cancer, providing a resource for exploring PTM crosstalk within and across proteins involved in the disease.