Aurora-B Promotes Osteosarcoma Cell Growth and Metastasis Through Activation of the NPM1/ERK/NF-κβ/MMPs Axis
| Autor: | Wen-Zhao Chen, Jia-Ming Liu, Ai-Fen Peng, Xin Wu, Honghai Song, Zhi-Li Liu, Yang Zhou |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway medicine.diagnostic_test Cell growth Chemistry macromolecular substances Matrix metalloproteinase medicine.disease Metastasis enzymes and coenzymes (carbohydrates) 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Oncology Western blot Apoptosis 030220 oncology & carcinogenesis embryonic structures medicine Cancer research Phosphorylation Osteosarcoma biological phenomena cell phenomena and immunity |
| Zdroj: | Cancer Management and Research. 12:4817-4827 |
| ISSN: | 1179-1322 |
| DOI: | 10.2147/cmar.s252847 |
| Popis: | Purpose Osteosarcoma (OS) is the most common primary malignant tumor of the bone in young adolescents and children. We explored the underlying mechanism of Aurora-B in promoting OS cell proliferation and metastasis. Patient and methods Bioinformatics was employed to predict the substrate of Aurora-B. IHC and Western blot were used to confirm the correlation between Aurora-B and NPM1. ERK/NF-κβ pathway-related proteins were detected by Western blot and immunofluorescence (IF). CCK8, wound healing, transwell, and Tunel assays were used to identify the cell proliferation, migration and apoptosis potential. Spontaneous metastasis xenografts were established to confirm the role of Aurora-B and NPM1. Results Aurora-B promotes NPM1 phosphorylation on Ser125. The phosphorylation of NPM1Ser125 induced by Aurora-B activates the ERK/NF-κβ signaling. Further study revealed that Aurora-B promotes proliferation, migration and inhibits apoptosis via phosphorylating NPM1 in vitro and in vivo. Conclusion Aurora-B promotes OS malignancy via phosphorylating NPM1Ser125 and activating ERK/NF-κβ signaling. |
| Databáze: | OpenAIRE |
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