دورية أكاديمية
TIPE2 inhibits the migration and invasion of epithelial ovarian cancer cells by targeting Smad2 to reverse TGF-β1-induced EMT.
| العنوان: | TIPE2 inhibits the migration and invasion of epithelial ovarian cancer cells by targeting Smad2 to reverse TGF-β1-induced EMT. |
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| المؤلفون: | Tang Z; Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P.R. China.; Department of Gynecology and Obstetrics, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China., Zhang D; Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P.R. China.; Department of Gynecology and Obstetrics, Jinan Third People's Hospital, Jinan, Shandong, P.R. China., Yao C; Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P.R. China.; Department of Gynecology and Obstetrics, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China., Jiang M; Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P.R. China.; Department of Gynecology and Obstetrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China., Wang C; Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P.R. China.; Department of Gynecology and Obstetrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China., Chen Z; Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P.R. China.; Department of Gynecology and Obstetrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China., Yu H; Department of Gynecology and Obstetrics, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China., Xue C; Department of Gynecology and Obstetrics, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China., Liu Y; Department of Gynecology and Obstetrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China., Shi Y; Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P.R. China., Zhang L; Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P.R. China., Wang X; Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P.R. China., Wei Z; Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P.R. China.; Department of Gynecology and Obstetrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China. |
| المصدر: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2024 Sep; Vol. 38 (17), pp. e70045. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Federation of American Societies for Experimental Biology Country of Publication: United States NLM ID: 8804484 Publication Model: Print Cited Medium: Internet ISSN: 1530-6860 (Electronic) Linking ISSN: 08926638 NLM ISO Abbreviation: FASEB J Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2020- : [Bethesda, Md.] : Hoboken, NJ : Federation of American Societies for Experimental Biology ; Wiley Original Publication: [Bethesda, Md.] : The Federation, [c1987- |
| مواضيع طبية MeSH: | Smad2 Protein*/metabolism , Smad2 Protein*/genetics , Epithelial-Mesenchymal Transition* , Transforming Growth Factor beta1*/metabolism , Intracellular Signaling Peptides and Proteins*/metabolism , Intracellular Signaling Peptides and Proteins*/genetics , Cell Movement* , Carcinoma, Ovarian Epithelial*/metabolism , Carcinoma, Ovarian Epithelial*/pathology , Carcinoma, Ovarian Epithelial*/genetics , Ovarian Neoplasms*/pathology , Ovarian Neoplasms*/metabolism , Ovarian Neoplasms*/genetics, Humans ; Female ; Cell Line, Tumor ; Animals ; Mice ; Neoplasm Invasiveness ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Mice, Inbred BALB C ; Signal Transduction |
| مستخلص: | Epithelial ovarian cancer is the deadliest gynecologic malignancy, characterized by high metastasis. Transforming growth factor-β1 (TGF-β1) drives epithelial- mesenchymal transformation (EMT), a key process in tumor metastasis. Tumor necrosis factor-α-induced protein 8 (TNFAIP8)-like 2 (TIPE2) acts as a negative regulator of innate and adaptive immunity and involves in various cancers. However, its relationship with TGF-β1 in ovarian cancer and its role in reversing TGF-β1-induced EMT remain unclear. This study examined TIPE2 mRNA and protein expression using quantitative RT-PCR (qRT-PCR), western blot and immunohistochemistry. The effects of TIPE2 overexpression and knockdown on the proliferation, migration and invasion of epithelial ovarian cancer cells were assessed through 5-ethynyl-2-deoxyuridine, colony-forming, transwell migration and invasion assays. The relationship between TIPE2 and TGF-β1 was investigated using qRT-PCR and enzyme-linked immunosorbent assay, while the interaction between TIPE2 and Smad2 was identified via co-immunoprecipitation. The results revealed that TIPE2 protein was significantly down-regulated in epithelial ovarian cancer tissues and correlated with the pathological type of tumor, patients' age, tumor differentiation degree and FIGO stage. TIPE2 and TGF-β1 appeared to play an opposite role to each other during the progression of human ovarian cancer cells. Furthermore, TIPE2 inhibited the metastasis and EMT of ovarian cancer cells by combining with Smad2 in vitro or in an intraperitoneal metastasis model. Consequently, these findings suggest that TIPE2 plays a crucial inhibitory role in ovarian cancer metastasis by modulating the TGF-β1/Smad2/EMT signaling pathway and may serve as a potential target for ovarian cancer, providing important direction for future diagnostic and therapeutic strategies. (© 2024 Federation of American Societies for Experimental Biology.) |
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| معلومات مُعتمدة: | ZR2018MH013 Natural Science Foundation of Shandong Province; ZR2023MH040 Natural Science Foundation of Shandong Province; 81771554 MOST | National Natural Science Foundation of China (NSFC); 81471437 MOST | National Natural Science Foundation of China (NSFC) |
| فهرسة مساهمة: | Keywords: Smad2‐EMT; TGF‐β1; TIPE2; migration and invasion; ovarian cancer |
| المشرفين على المادة: | 0 (Smad2 Protein) 0 (Transforming Growth Factor beta1) 0 (Intracellular Signaling Peptides and Proteins) 0 (SMAD2 protein, human) 0 (TNFAIP8L2 protein, human) 0 (TGFB1 protein, human) |
| تواريخ الأحداث: | Date Created: 20240911 Date Completed: 20240911 Latest Revision: 20240916 |
| رمز التحديث: | 20240917 |
| DOI: | 10.1096/fj.202401427R |
| PMID: | 39259551 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1530-6860 |
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| DOI: | 10.1096/fj.202401427R |