Targeting Aurora-A Inhibits Tumor Progression and Sensitizes Thyroid Carcinoma to Sorafenib by Decreasing PFKFB3-mediated Glycolysis

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2023 Mar 29

PMID 36990998

Authors

Zhi Jingtai

Hu Linfei

Qian Yuyang

Kang Ning

Yun Xinwei

Wang Xin

Ruan Xianhui

Huang Dongmei

Yang Weiwei

Meng Xiangrui

Zhu Tianze

Wang Wei

Zheng Xiangqian

Affiliations

Soon will be listed here.

Abstract

Thyroid cancer (TC) is the most common endocrine tumor, amongst which anaplastic thyroid carcinoma (ATC) is the most deadly. Aurora-A usually functions as oncogenes, and its inhibitor Alisertib exerts a powerful antitumor effect in various tumors. However, the mechanism of Aurora-A in regulating TC cell energy supply remains unclear. In the present study, we demonstrated the antitumor effect of Alisertib and an association between high Aurora-A expression and shorter survival. Multi-omics data and in vitro validation data suggested that Aurora-A induced PFKFB3-mediated glycolysis to increase ATP supply, which significantly upregulated the phosphorylation of ERK and AKT. Furthermore, the combination of Alisertib and Sorafenib had a synergistic effect, further confirmed in xenograft models and in vitro. Collectively, our study provides compelling evidence of the prognostic value of Aurora-A expression and suggests that Aurora-A upregulates PFKFB3-mediated glycolysis to enhance ATP supply and promote TC progression. Combining Alisertib with Sorafenib has huge prospects for application in treating advanced thyroid carcinoma.

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