ArticleCancer letters2017
PAD1 promotes epithelial-mesenchymal transition and metastasis in triple-negative breast cancer cells by regulating MEK1-ERK1/2-MMP2 signaling.
Article in Cancer letters, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review.Frontiers in immunology · 2023Pooled it
- Anti-gingipain antibodies and ACE1 activity in rheumatoid arthritis: associations with disease activity and cardiovascular comorbidity in a cross-sectional study.Rheumatology international · 2026Article
- Discovery of highly potent naphthalene/quinoline-based PAD inhibitors: Structure-activity relationship, selectivity, and cytotoxicity.European journal of medicinal chemistry · 2025Article
- Citrullination of AKT2 Catalyzed by PAD1 Facilitates the Maintenance of Stemness Characteristics of Ovarian Cancer Stem-Like Cells in Ovarian Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Citrullination in health and disease: From physiological function to gene regulation.Genes & diseases · 2025Review
- Macrophage invasion into the Drosophila brain requires JAK/STAT-dependent MMP activation in the blood-brain barrier.PLoS biology · 2025Article
- Targeting PADI2 as a potential therapeutic strategy against metastasis in oral cancer via suppressing EMT-mediated migration and invasion and CCL3/5-induced angiogenesis.Clinical & experimental metastasis · 2024Article
- TDERS, an exosome RNA-derived signature predicts prognosis and immunotherapeutic response in clear cell renal cell cancer: a multicohort study.Journal of the National Cancer Center · 2024Article
- Application of integrin subunit genes in pancreatic cancer and the construction of a prognosis model.Journal of gastrointestinal oncology · 2024Article
- Brain-Region-Specific Differences in Protein Citrullination/Deimination in a Pre-Motor Parkinson's Disease Rat Model.International journal of molecular sciences · 2024Article
- Citrullination and the protein code: crosstalk between post-translational modifications in cancer.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Inhibiting MEK1 R189 citrullination enhances the chemosensitivity of docetaxel to multiple tumour cells.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- Current insights into the role of citrullination in thrombosis.Current opinion in chemical biology · 2023Review
- Selective inhibition of peptidyl-arginine deiminase (PAD): can it control multiple inflammatory disorders as a promising therapeutic strategy?Inflammopharmacology · 2023Review
- Low temperature plasma suppresses proliferation, invasion, migration and survival of SK-BR-3 breast cancer cells.Molecular biology reports · 2023Article
- Differential Protein Citrullination in Human ER- and ER+ Tumor and Adjacent Healthy Breast Tissue.Biochemistry · 2023Article
- PPP1R14D promotes the proliferation, migration and invasion of lung adenocarcinoma via the PKCα/BRAF/MEK/ERK signaling pathway.International journal of oncology · 2022Article
- PAD4 and Its Inhibitors in Cancer Progression and Prognosis.Pharmaceutics · 2022Review
- PAD4-dependent citrullination of nuclear translocation of GSK3β promotes colorectal cancer progression via the degradation of nuclear CDKN1A.Neoplasia (New York, N.Y.) · 2022Article
- A Pilot Study on Peptidylarginine Deiminases and Protein Deimination in Animal Cancers across Vertebrate Species.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Peptidylargininedeiminase 1 (PAD1) catalyzes protein for citrullination, and this activity has been linked to the epidermal cornification. However, a role for PAD1 in tumorigenesis, including breast cancers has not been previously explored. Here we first showed that PAD1 is overexpressed in human triple negative breast cancer (TNBC). In cultured cells and xenograft mouse models, PAD1 depletion or inhibition reduced cell proliferation, suppressed epithelial-mesenchymal transition, and prevented metastasis of MDA-MB-231 cells. These changes were correlated with a dramatic decrease in MMP2/9 expression. Furthermore, ERK1/2 and P38 MAPK signaling pathways are activated upon PAD1 silencing. Treatment with MEK1/2 inhibitor in PAD1 knockdown cells significantly recovered MMP2 expression, while inhibiting P38 activation only slightly elevated MMP9 levels. We then showed that PAD1 interacts with and citrullinates MEK1 thereby disrupting MEK1-catalyzed ERK1/2 phosphorylation, thus leading to the MMP2 overexpression. Collectively, our data indicate that PAD1 appears to promote tumorigenesis by regulating MEK1-ERK1/2-MMP2 signaling in TNBC. These results also raise the possibility that PAD1 may function as an important new biomarker for TNBC tumors and suggest that PAD1-specific inhibitors could potentially be utilized to treat metastatic breast cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.