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Targeting PADI2 as a potential therapeutic strategy against metastasis in oral cancer via suppressing EMT-mediated migration and invasion and CCL3/5-induced angiogenesis.

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العنوان: Targeting PADI2 as a potential therapeutic strategy against metastasis in oral cancer via suppressing EMT-mediated migration and invasion and CCL3/5-induced angiogenesis.
المؤلفون: Hung SK; Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan.; School of Medicine, Tzu Chi University, Hualien, Taiwan., Yu CC; Department of Medical Research, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan., Lin HY; Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan.; School of Medicine, Tzu Chi University, Hualien, Taiwan., Chiou WY; Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan.; School of Medicine, Tzu Chi University, Hualien, Taiwan., Lee MS; Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan.; School of Medicine, Tzu Chi University, Hualien, Taiwan., Lin RI; Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan., Lu MC; School of Medicine, Tzu Chi University, Hualien, Taiwan. e360187@yahoo.com.tw.; Department of Medical Research, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan. e360187@yahoo.com.tw.; Division of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 2, Min-Sheng Road, Dalin, Chiayi, 62247, Taiwan. e360187@yahoo.com.tw.
المصدر: Clinical & experimental metastasis [Clin Exp Metastasis] 2024 Aug 31. Date of Electronic Publication: 2024 Aug 31.
Publication Model: Ahead of Print
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Kluwer Academic Publishers Country of Publication: Netherlands NLM ID: 8409970 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-7276 (Electronic) Linking ISSN: 02620898 NLM ISO Abbreviation: Clin Exp Metastasis Subsets: MEDLINE
أسماء مطبوعة: Publication: Dordrecht : Kluwer Academic Publishers
Original Publication: London : Taylor & Francis, c1983-
مستخلص: Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive malignancy, with metastasis being the leading cause of death in patients. Unfortunately, therapeutic options for metastatic OSCC remain limited. Peptidylarginine deiminases (PADI) are implicated in various tumorigenesis and metastasis processes across multiple cancers. However, the role of PADI2, a type of PADI, in OSCC is not well understood. This study aimed to explore the impact of PADI2 on epithelial-mesenchymal transition (EMT), angiogenesis, and OSCC metastasis. The effect of PADI2 on EMT was evaluated using cell lines by Western blot analysis with shRNA targeting PADI2. In addition, the selective PADI2 inhibitor AFM32a was used to assess the effect of PADI2 on cancer metastasis and angiogenesis in animal models. Our findings indicated that PADI2 expression correlated with EMT changes, and PADI2 knockdown reversed these changes, reducing cell proliferation, cell migration, and invasion. PADI2 inhibition also diminished tube formation in HUVECs and decreased secretion of angiogenesis-related chemokines CCL3, CCL5 and CCL20. In a mouse model, AFM32a markedly reduced lung metastasis and production of CCL3 and CCL5. Our in vitro and in vivo studies suggested inhibiting PADI2 could prevent OSCC metastasis by impeding EMT and angiogenesis via AKT/mTOR signaling pathway. These results highlight PADI2 as a potential therapeutic target for combating OSCC metastasis.
(© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
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معلومات مُعتمدة: (DTCRD111(2)-I-02, DTCRD112(2)-I-06, DTCRD112-E-05). Buddhist Dalin Tzu Chi Hospital
فهرسة مساهمة: Keywords: Angiogenesis; Epithelial-mesenchymal transition; Metastasis; Oral squamous cell carcinoma; Peptidylarginine deiminases type 2
تواريخ الأحداث: Date Created: 20240831 Latest Revision: 20240831
رمز التحديث: 20240902
DOI: 10.1007/s10585-024-10310-5
PMID: 39215870
قاعدة البيانات: MEDLINE
الوصف
تدمد:1573-7276
DOI:10.1007/s10585-024-10310-5