AURKB activates EMT through PI3K/AKT signaling axis to promote ICC progression

Abstract

Intrahepatic cholangiocarcinoma (ICC) is a fatal disease and the molecular mechanism of its progression is unknown. Aurora Kinase B (AURKB) is a central regulator of chromosome separation and cytokinesis and is abnormally expressed in a variety of cancer cells. This research aimed to explore the effect of AURKB in occurrence and metastasis of ICC. We found that AURKB showed a progressive up-regulation pattern from normal bile duct tissue to ICC with high invasion. Our data showed that AURKB significantly promoted ICC cell proliferation, induced epithelial-mesenchymal transition (EMT), migration and invasion through gain- and loss- of function experiments. In vivo results consistently showed that AURKB up-regulation not only promoted tumor growth, but also promoted tumor metastasis. Importantly, we discovered that AURKB regulates the expressions of EMT-related genes via PI3K/AKT signaling axis. Thus, our results suggest that AURKB induced EMT through the activation of PI3K/AKT signaling pathway is critical to the progression of ICC, which may be a prospective therapeutic treatment for overcoming ICC metastasis and progression.

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“…AURKB is also involved in different molecular pathways when dysregulated. For example, one study showed that overexpression of this mitotic kinase can activate the PI3K/AKT signaling pathway in intrahepatic cholangiocarcinoma [85]. Activating this pathway can promote EMT by increasing the expression levels of N-cadherin and Vimentin.…”