Anticancer Peptidylarginine Deiminase (PAD) Inhibitors Regulate the Autophagy Flux and the Mammalian Target of Rapamycin Complex 1 Activity

Background: Histone citrullination by PAD4 regulates tumor suppressor gene expression.Results: The novel PAD inhibitor YW3-56 inhibits cancerous growth by perturbing autophagy and regulating the SESN2-mTORC1 signaling axis.Conclusion: YW3-56 regulates the SESN2-mTORC1 autophagy pathway as one of its anticancer mechanisms.Significance: This study identifies a novel function of PAD4 in the autophagy pathway and developed potent PAD inhibitors for future cancer research.