The Role of Peptidyl Arginine Deiminase IV(PADI4) in Cancers

Background: Peptidyl arginine deiminase IV (PADI4, also called PAD4), a Ca²⁺-dependent posttranslational modification enzyme, catalyzes the conversion of arginine residues to non-coded citrulline residues. Dysregulation of PADI4 is involved in a variety of diseases including rheumatoid arthritis (RA), multiple sclerosis (MS), Alzheimer's disease (AD) and many kinds of malignant tumors. Objective: The roles of PADI4 in different tumors and the underlying molecular mechanisms are presented in this article. Results: PADI4-mediated citrullination is associated with either transcriptional activation or repression in different contexts. Abnormal expression of PADI4 exists in a variety of malignant tumors and affects tumor progression and metastasis. Epithelial-to-mesenchymal transition (EMT), apoptosis, and neutrophil extracellular traps (NETs) may be the underlying molecular mechanisms. Conclusion: PADI4 plays crucial role in the occurrence, development, and metastasis of tumors, and PADI4 may be an effective biomarker for cancer prognosis and a potential target for cancer treatment.