极光激酶B通过激活NPM1/ERK/NF-κβ/基质金属蛋白酶轴促进骨肉瘤细胞生长和转移。
Aurora-B Promotes Osteosarcoma Cell Growth and Metastasis Through Activation of the NPM1/ERK/NF-κβ/MMPs Axis.
作者信息
Song Honghai, Zhou Yang, Peng Aifen, Liu Jiaming, Wu Xin, Chen Wenzhao, Liu Zhili
机构信息
Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People's Republic of China.
Institute of Spinal and Spinal Cord Diseases, Nanchang University, Nanchang 330031, People's Republic of China.
出版信息
Cancer Manag Res. 2020 Jun 23;12:4817-4827. doi: 10.2147/CMAR.S252847. eCollection 2020.
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 NPM1 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 NPM1 and activating ERK/NF-κβ signaling.
目的
骨肉瘤（OS）是青少年和儿童中最常见的原发性骨恶性肿瘤。我们探讨了Aurora-B促进OS细胞增殖和转移的潜在机制。
患者与方法
采用生物信息学方法预测Aurora-B的底物。免疫组化（IHC）和蛋白质印迹法用于确认Aurora-B与核仁磷酸蛋白1（NPM1）之间的相关性。通过蛋白质印迹法和免疫荧光（IF）检测细胞外信号调节激酶（ERK）/核因子κB（NF-κβ）信号通路相关蛋白。采用细胞计数试剂盒-8（CCK8）、伤口愈合实验、Transwell实验和Tunel实验来鉴定细胞的增殖、迁移和凋亡潜能。建立自发转移异种移植模型以证实Aurora-B和NPM1的作用。
结果
Aurora-B促进NPM1第125位丝氨酸（Ser125）的磷酸化。Aurora-B诱导的NPM1磷酸化激活ERK/NF-κβ信号。进一步研究表明，在体外和体内，Aurora-B通过使NPM1磷酸化促进增殖、迁移并抑制凋亡。
结论
Aurora-B通过使NPM1磷酸化并激活ERK/NF-κβ信号促进骨肉瘤的恶性进展。
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