PADs in cancer: Current and future

Abstract

Protein arginine deiminases (PADs), is a group of calcium-dependent enzymes, which play crucial roles in citrullination, and can catalyze arginine residues into citrulline. This chemical reaction induces citrullinated proteins formation with altered structure and function, leading to numerous pathological diseases, including inflammation and autoimmune diseases. To date, multiple studies have provided solid evidence that PADs are implicated in cancer progression. Nevertheless, the findings on PADs functions in tumors are too complex to understand due to its involvements in variable signaling pathways. The increasing interest in PADs has heightened the need for a comprehensive description for its role in cancer. The present study aims to identify the gaps in present knowledge, including its structures, biological substrates and tissue distribution. Since several irreversible inhibitors for PADs with good potency and selectivity have been explored, the mechanisms on the dysregulation in tumors remain poorly understood. The present study discusses the relationship between PADs and tumor apoptosis, EMT formation and metastasis as well as the implication of neutrophil extracellular traps (NETs) in tumorigenesis. In addition, the potential uses of citrullinated antigens for immunotherapy were proposed.

Keywords: Apoptosis; Epithelial-to-mesenchymal transition (EMT); Immunity; Neutrophil extracellular traps (NETs); Protein arginine deiminases (PADs); Tumor.