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Updated: Aug 22, 2025

Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog
Published on: November 5, 2014
PAD4 and Its Inhibitors in Cancer Progression and Prognosis
Di Zhu1,2, Yu Lu1,2, Yanming Wang3
1Department of Medicinal Chemistry, College of Pharmaceutical Sciences of Capital Medical University, Beijing 100069, China.
Abstract:
The systemic spread of malignancies and the risk of cancer-associated thrombosis are major clinical challenges in cancer therapy worldwide. As an important post-translational modification enzyme, peptidyl arginine deiminase 4 (PAD4) could mediate the citrullination of protein in different components (including nucleus and cytoplasm, etc.) of a variety of cells (tumor cells, neutrophils, macrophages, etc.), thus participating in gene regulation, neutrophil extracellular trap (NET) and macrophage extracellular trap (MET). Thereby, PAD4 plays an important role in enhancing the growth of primary tumors and facilitating the distant metastasis of cancer cells. In addition, it is related to the formation of cancer-associated thrombosis. Therefore, the development of PAD4-specific inhibitors may be a promising strategy for treating cancer, and it may improve patient prognosis. In this review, we describe PAD4 involvement in gene regulation, protein citrullination, and NET formation. We also discuss its potential role in cancer and cancer-associated thrombosis, and we summarize the development and application of PAD4 inhibitors.
Insights
Peptidyl arginine deiminase 4 (PAD4) drives cancer growth, metastasis, and thrombosis. Inhibiting PAD4 shows promise for improving cancer treatment and patient outcomes.
Area of Science:
- Biochemistry
- Oncology
- Immunology
Background:
- Systemic spread of malignancies and cancer-associated thrombosis are significant clinical challenges.
- Peptidyl arginine deiminase 4 (PAD4) is a post-translational modification enzyme involved in protein citrullination.
- PAD4 participates in gene regulation, neutrophil extracellular trap (NET), and macrophage extracellular trap (MET) formation.
Purpose of the Study:
- To review PAD4's role in gene regulation, protein citrullination, and NET formation.
- To discuss PAD4's involvement in cancer progression and cancer-associated thrombosis.
- To summarize the development and application of PAD4 inhibitors for cancer therapy.
Main Methods:
- Literature review of PAD4's functions and involvement in cancer.
- Analysis of PAD4's role in cellular processes like citrullination and trap formation.
- Summary of existing and developing PAD4 inhibitors.
Main Results:
- PAD4 enhances primary tumor growth and distant cancer cell metastasis.
- PAD4 is implicated in the pathogenesis of cancer-associated thrombosis.
- PAD4 inhibitors represent a potential therapeutic strategy for cancer treatment.
Conclusions:
- PAD4 is a key mediator in cancer progression and thrombosis.
- Targeting PAD4 offers a promising avenue for novel cancer therapies.
- PAD4 inhibitors may improve patient prognosis in cancer treatment.
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