Phosphoproteomic and Acetylomic Characterization of Colorectal Cancer Cells Treated with Kinase Inhibitors

Kinase inhibitors have long been studied to be developed into therapeutic drugs or chemical probes, but their off-target effects in phosphoproteomics and acetylomics remain largely unexplored. Here, we provided a systematic molecular response to kinase inhibitors in the colorectal cancer cell line, including the proteomics, phosphoproteomics, and acetylomics. The results provided comprehensive kinase activity perturbations of each kinase inhibitor and presented unique pathway-level biological effects, mitochondrial functional perturbations, and kinase activity changes for inhibitors targeting the same pathway. Furthermore, we discovered the potential protein post-translational modification (PTM) crosstalk between lysine acetylation and protein phosphorylation. The study additionally proposed potential combination treatment strategies. In summary, this study presented in-depth and comprehensive analysis results of kinase inhibitor perturbations on the colorectal cancer cell line at proteomic, phosphoproteomic, and acetylomic landscapes.