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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2021 | Metastasis | Research

Inhibiting the redox function of APE1 suppresses cervical cancer metastasis via disengagement of ZEB1 from E-cadherin in EMT

Authors: Qing Li, Zhi-Wei Zhou, Wei Duan, Cheng-Yuan Qian, Shu-Nan Wang, Meng-Sheng Deng, Dan Zi, Jian-Min Wang, Cheng-Yi Mao, Guanbin Song, Dong Wang, Kenneth D. Westover, Cheng-Xiong Xu

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2021

Abstract

Background

Metastasis is a major challenge in cervical cancer treatment. Previous studies have shown that the dual functional protein apurinic/apyrimidinic endonuclease 1 (APE1) promotes tumor metastasis and is overexpressed in cervical cancer. However, the biological role and mechanism of APE1 in cervical cancer metastasis have rarely been studied.

Methods

We used gene set enrichment analysis (GSEA) to determine the APE1-related signaling pathways in cervical cancer. To investigate the role and mechanism of APE1 in cervical cancer metastasis and invasion, immunohistochemistry, immunofluorescence, western blotting, secondary structure prediction, coimmunoprecipitation, luciferase reporter, and electrophoretic mobility shift assays were performed. The inhibitory effects of the APE1 redox function inhibitor APX3330 on cervical cancer metastasis were evaluated using animal models.

Results

Clinical data showed that high expression of APE1 was associated with lymph node metastasis in cervical cancer patients. GSEA results showed that APE1 was associated with epithelial to mesenchymal transition (EMT) in cervical cancer. Ectopic expression of APE1 promoted EMT and invasion of cervical cancer cells, whereas inhibition of APE1 suppressed EMT and invasion of cervical cancer cells in a redox function-dependent manner. Notably, APE1 redox function inhibitor APX3330 treatment dramatically suppressed cervical cancer cell lymph node and distant metastasis in vivo. Furthermore, we found that APE1 enhanced the interaction between ZEB1 and the E-cadherin promoter by binding to ZEB1, thereby suppressing the expression of E-cadherin, a negative regulator of EMT.

Conclusion

Our findings help to elucidate the role played by APE1 in cervical cancer metastasis and targeting APE1 redox function may be a novel strategy for inhibiting cervical cancer metastasis.

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Title: Inhibiting the redox function of APE1 suppresses cervical cancer metastasis via disengagement of ZEB1 from E-cadherin in EMT
Authors: Qing Li
Zhi-Wei Zhou
Wei Duan
Cheng-Yuan Qian
Shu-Nan Wang
Meng-Sheng Deng
Dan Zi
Jian-Min Wang
Cheng-Yi Mao
Guanbin Song
Dong Wang
Kenneth D. Westover
Cheng-Xiong Xu
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Metastasis
Cervical Cancer
Cervical Cancer
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2021
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-021-02006-5

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Abstract

Background

Methods

Results

Conclusion

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