Aurora kinase a promotes the progression of papillary thyroid carcinoma by activating the mTORC2-AKT signalling pathway

Aurora激酶a通过激活mTORC2-AKT信号通路促进乳头状甲状腺癌的进展

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作者:Zewei Zhao #, Huijuan Wang #, Ning Kang #, Zhongyu Wang, Xiukun Hou, Linfei Hu, Shuo Qie, Jianping Guo, Songfeng Wei, Xianhui Ruan, Xiangqian Zheng

Background

Treatment failure is the main cause of death from papillary thyroid carcinoma (PTC). It is urgent to look for new intervention targets and to develop new therapies for treating PTC. Aurora-A kinase (AURKA) functionally regulates cell mitosis and is closely related to the occurrence and development of a variety of tumours. However, the expression and potential functions of AURKA in PTC remain largely elusive.

Conclusions

We found that AURKA plays critical roles in regulating the progression of PTC by activating the mTORC2-AKT pathway, highlighting the potential of targeting AURKA to treat PTC.

Results

Clinicopathologically, AURKA is highly expressed in PTC tissues compared to normal tissues and is correlated with lymph node metastasis, TNM stage and patient prognosis. Biologically, AURKA functions as an oncoprotein to promote the proliferation and migration of PTC cells. Mechanistically, AURKA directly binds to SIN1 and compromises CUL4B-based E3 ligase-mediated ubiquitination and subsequent degradation of SIN1, leading to hyperactivation of the mTORC2-AKT pathway in PTC cells. Conclusions: We found that AURKA plays critical roles in regulating the progression of PTC by activating the mTORC2-AKT pathway, highlighting the potential of targeting AURKA to treat PTC.

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