CUL1 Knockdown Attenuates the Adhesion, Invasion, and Migration of Triple-Negative Breast Cancer Cells via Inhibition of Epithelial-Mesenchymal Transition
| العنوان: | CUL1 Knockdown Attenuates the Adhesion, Invasion, and Migration of Triple-Negative Breast Cancer Cells via Inhibition of Epithelial-Mesenchymal Transition |
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| المؤلفون: | Xiuzhong Zhang, Wen-Jing Yan, Shou-Kun Chen, Chong Zhang, Zeqiang Ren, Pengbo Zhang |
| المصدر: | Pathology & Oncology Research. 26:1153-1163 |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Epithelial-Mesenchymal Transition, Triple Negative Breast Neoplasms, Cell morphology, Pathology and Forensic Medicine, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Cell Movement, Cell Line, Tumor, Cell Adhesion, medicine, Humans, Neoplasm Invasiveness, Epithelial–mesenchymal transition, Epidermal growth factor receptor, Protein kinase B, Triple-negative breast cancer, Gene knockdown, biology, Chemistry, General Medicine, Cullin Proteins, medicine.disease, 030104 developmental biology, Oncology, Gene Knockdown Techniques, 030220 oncology & carcinogenesis, Cancer research, biology.protein, Female |
| الوصف: | Cullin-1 (CUL1) is an important factor for tumor growth and a potential therapeutic target for breast cancer therapy, but the molecular mechanism in triple-negative breast cancer (TNBC) is unknown. In the present study, CUL1 shRNA was transfected into BT549 and MDA-MB-231 breast cancer cells. Cell morphology, adhesion, invasion, and migration assays were carried out in the CUL1 knockdown cells. Additionally, protein expression levels of epithelial-mesenchymal transition (EMT)-related factors, Akt phosphorylation at S473 (pAkt), glycogen synthase kinase-3β phosphorylation at ser9 (pGSK3β), cytoplasmic and nuclear β-catenin, and epidermal growth factor receptor phosphorylation at Tyr1068 (pEGFR) were detected by Western blot analysis. CUL1 knockdown significantly suppressed the adhesion, invasion and migration capabilities of the cells, and decreased the expression of Snail1/2, ZEB1/2, Twist1/2, Vimentin, and increased the expression of Cytokeratin 18 (CK18). Moreover, CUL1 knockdown significantly downregulated the phosphorylated levels of Akt, GSK3β, and EGFR, inhibiting the translocation of β-catenin from the cytoplasm to the nucleus. The results indicate that CUL1 knockdown prohibited the metastasis behaviors of breast cancer cells through downregulation (dephosphorylation) of the EMT signaling pathways of EGFR and Akt/GSK3β/β-catenin in breast cancer. These results strongly suggested that reinforcement of the EMT might be a key for CUL1 to accelerate TNBC metastasis. |
| تدمد: | 1532-2807 1219-4956 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::635768e450d98871ef07252127be992cTest https://doi.org/10.1007/s12253-019-00681-6Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....635768e450d98871ef07252127be992c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15322807 12194956 |
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