Dysregulated citrullination is thought to be a significant contributor to the pathogenesis of numerous diseases such as rheumatoid arthritis but has not been largely studied in cancer, specifically in the breast. Post-translational modification of arginine residues to citrulline is catalyzed by members of the peptidylarginine deiminase (PAD) family. We developed an LC-UV method to measure PAD activity and utilized an MS-based proteomics approach to investigate differential protein citrullination in ER- and ER+ breast tumor tissue compared to healthy adjacent tissue. We optimized three different peptides (gastrin-releasing peptide, glucagon-like peptide, and insulin) to measure the ability of PAD to citrullinate its substrate and using our LC-UV method, we report that both citrullinated and non-citrullinated peptides were distinguishable based on their retention time. In addition, we report 72 and 41 proteins citrullinated in ER- tumor and adjacent healthy tissue, respectively, where 20 of these proteins are shared between the two. For ER+ tumor and adjacent healthy tissue, we detected 64 and 49 citrullinated proteins, respectively, where 32 proteins are shared. Interestingly, when comparing ER- and ER+ tumor tissue, 32 citrullinated proteins are shared between the two and the rest are unique to the tumor’s receptor status. Further research is needed on protein citrullination and role of this unique post-translational modification in cancer biology.

Comparing the citrullinome between human ER- and ER+ tumor and adjacent healthy breast tissue

ACS Spring Meeting 2021

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