A Novel Selective Inhibitor JBI-589 Targets PAD4-Mediated Neutrophil Migration to Suppress Tumor Progression.

ABSTRACT: Neutrophils are closely involved in the regulation of tumor progression and formation of premetastatic niches. However, the mechanisms of their involvement and therapeutic regulation of these processes remain elusive. Here, we report a critical role of neutrophil peptidylarginine deiminase 4 (PAD4) in neutrophil migration in cancer. In several transplantable and genetically engineered mouse models, tumor growth was accompanied by significantly elevated enzymatic activity of neutrophil PAD4. Targeted deletion of PAD4 in neutrophils markedly decreased the intratumoral abundance of neutrophils and led to delayed growth of primary tumors and dramatically reduced lung metastases. PAD4-mediated neutrophil accumulation by regulating the expression of the major chemokine receptor CXCR2. PAD4 expre

SUBMITTER: Deng H 

PROVIDER: S-EPMC9532374 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature