Aurora-B: a novel biomarker in the invasion and metastasis of osteosarcoma

Abstract

Osteosarcoma (OS), a primary human malignant tumor that affects the bones, mostly arises in children and adolescents. Even though surgical resection followed by radiotherapy and chemotherapy has improved the survival rate up to 60%, the long-term positive effect for most patients with OS is not satisfactory. Hence, elucidating the specific mechanisms involved in the pathogenesis of OS is particularly important. Aurora-B, a serine/threonine kinase, plays a crucial role in centrosome regulation, spindle formation and chromosomal separation during mitosis. It has been found that Aurora-B overexpression is related to the occurrence and development of several malignant tumors, including OS. This article summarizes the role of Aurora-B in the invasion and metastasis of OS.

Keywords: Aurora-B; biomarker; invasion; metastasis; osteosarcoma.

Figure 1.

The role of Aurora-B in the invasion and metastasis of OS (By Figdraw). (A) Aurora-B mediates NPM1 phosphorylation, activating the ERK/NF-κβ signaling pathway. The activation of NF-κβ initiates MMP-2 and MMP-9 transcription, promoting the invasion and metastasis of OS. (B) Let-7a downregulates Aurora-B expression, inhibiting NF-κβ/MMP signaling pathway. The decrease of MMP-2 and MMP-9 proteins prevents the malignant progression of OS. (C) Inhibiting Aurora-B influences the PI3K/Akt signaling pathway, reducing the Akt phosphorylation. Low p-Akt inhibites the expression of NF-κB, which in turn prevents the progression of OS. PETN: pentaerythrityl tetranitrate (a compound dephosphorylating PIP3); PI3K: a kinase phosphorylating PIP2. (D) Silence of Aurora-B promotes AMPK phosphorylation and ULK1 expression, while inhibits mTOR expression. The alteration of AMKP/mTOR/ULK1 signaling pathway activates autophagy, preventing the development of OS. MHY1485: a mTOR activator.