Aurora-B Promotes Osteosarcoma Cell Growth and Metastasis Through Activation of the NPM1/ERK/NF-κβ/MMPs Axis

Honghai Song; Yang Zhou; Aifen Peng; Jiaming Liu; Xin Wu; Wenzhao Chen; Zhili Liu

doi:10.2147/CMAR.S252847

Aurora-B Promotes Osteosarcoma Cell Growth and Metastasis Through Activation of the NPM1/ERK/NF-κβ/MMPs Axis

Cancer Manag Res. 2020 Jun 23:12:4817-4827. doi: 10.2147/CMAR.S252847. eCollection 2020.

Authors

Honghai Song^#^{1

2}, Yang Zhou^#¹, Aifen Peng³, Jiaming Liu^{1

2

4}, Xin Wu¹, Wenzhao Chen¹, Zhili Liu^{1

2

5}

Affiliations

¹ Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People's Republic of China.
² Institute of Spinal and Spinal Cord Diseases, Nanchang University, Nanchang 330031, People's Republic of China.
³ College of Humanities, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330004, People's Republic of China.
⁴ Jiangxi Institute of Respiratory Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
⁵ Division of Science and Technology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.

^# Contributed equally.

Abstract

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^Ser125 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^Ser125 and activating ERK/NF-κβ signaling.

Keywords: Aurora-B; ERK; NF-κβ; NPM1; osteosarcoma.

Grants and funding

This work is supported by the Natural Science Foundation of Jiangxi Province, PR. China (No. 20161ACB20011), the National Natural Science Foundation of China (No. 81560435) and the Department of Science and Technology Program of Jiangxi Province, China (No. 20162BCB23057).