Quantitative proteome and lysine succinylome analyses provide insights into metabolic regulation in breast cancer

Breast cancer, the most common invasive cancer and cause of cancer-related death in women worldwide, is a multifactorial, complex disease, and many molecular players and mechanisms underlying the complexity of its clinical behavior remain unknown. To explore the molecular features of breast cancer, quantitative proteome and succinylome analyses in breast cancer were extensively studied using quantitative proteomics techniques, anti-succinyl lysine antibody-based affinity enrichment, and high-resolution LC–MS/MS analysis. Our study is the first to detect the regulation of lysine succinylation in breast cancer progression. We identified a novel mechanism by which the pentose phosphate pathway and the endoplasmic reticulum protein processing pathway might be regulated via lysine succinylation in their core enzymes. These results expand our understanding of tumorigenesis mechanisms and provide a basis for further characterization of the pathophysiological roles in breast cancer progression, laying a foundation for innovative and novel breast cancer drugs and therapies.