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Aurora-A Induces Chemoresistance Through Activation of the AKT/mTOR Pathway in Endometrial Cancer.


ABSTRACT: Endometrial cancer (EC) is the most common gynecological tumor all over the world, and advanced/metastatic EC remains a malignancy with poor survival outcome due to highly resistant to conventional chemotherapeutic treatment. Here, we report that Aurora-A, a serine-threonine kinase, plays a vital role in chemoresistance of EC. Aurora-A is overexpressed in EC tissues, compared with normal endometrium and Aurora-A expression is associated with decreased overall survival. Overexpression of Aurora-A in EC cell lines (Ishikawa and HEC-1B cells) promotes cell proliferation and induced paclitaxel- and cisplatin-resistance. Furthermore, Aurora-A activating AKT-mTOR pathway further induces chemoresistance in vitro, consistent with a positive correlation between Aurora-A and phosphorylated AKT/4E-BP1 expression in EC tissues. In summary, our study provides the strong evidence that Aurora-A controls the sensitivity of EC cell lines to chemotherapy via AKT/mTOR pathway, indicating that pharmacologic intervention of Aurora-A and AKT/mTOR in combination with chemotherapy may be considered for the targeted therapy against EC with overexpression of Aurora-A.

SUBMITTER: Wu J 

PROVIDER: S-EPMC6540875 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Aurora-A Induces Chemoresistance Through Activation of the AKT/mTOR Pathway in Endometrial Cancer.

Wu Jun J   Cheng Ziyun Z   Xu Xiaofeng X   Fu Jian J   Wang Kaiyue K   Liu Tao T   Wu Chan C   Kong Xiangyi X   Yang Qian Q   Yan Guijun G   Zhou Huaijun H  

Frontiers in oncology 20190522


Endometrial cancer (EC) is the most common gynecological tumor all over the world, and advanced/metastatic EC remains a malignancy with poor survival outcome due to highly resistant to conventional chemotherapeutic treatment. Here, we report that Aurora-A, a serine-threonine kinase, plays a vital role in chemoresistance of EC. Aurora-A is overexpressed in EC tissues, compared with normal endometrium and Aurora-A expression is associated with decreased overall survival. Overexpression of Aurora-A  ...[more]

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