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The significance of EphA2-regulated Wnt/β-catenin signal pathway in promoting the metastasis of HBV-related hepatocellular carcinoma

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Abstract

Background

Hepatitis B virus (HBV) infection is closely associated with the malignant progression of hepatocellular carcinoma (HCC). However, the mechanism involved in the HBV-related HCC development remains poorly understood. Hence, the aim of this study is to investigate the regulatory mechanism of EphA2-induced epithelial-mesenchymal transition (EMT) in the metastasis of HBV-related HCC cells.

Methods and results

The expression level of EphA2 was determined in HBV-related human HCC cells. Then, the effects of EphA2 silencing on the EMT-associated proteins, the Wnt/β-catenin signal pathway and the metastatic potential of HBV-related HCC cells were evaluated. Finally, the inhibitory role of Entecavir (a potent antiviral drug for HBV) on EphA2-induced EMT was explored. The present study revealed that the EphA2 expression level was increased in HBV-related HCC cells compared with non-related HCC cells. Following EphA2 knockdown, the downregulation of Vimentin, β-catenin and p-GSK-3βSer9 expressions, the upregulation of E-cadherin expression, and the suppressed migration and invasion ability of HBV-related HCC cells were found. Additionally, Entecavir was proved to have a significant inhibitory effect on EphA2-induced EMT via attenuating the Wnt/β-catenin signal pathway.

Conclusions

In this study, we found that EphA2-induced EMT was involved in the enhanced metastatic potential of HBV-related HCC cells through the activation of the Wnt/β-catenin signal pathway.

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Acknowledgements

This work was supported by grants from the Key Project of Tian** Science and Technology Support Programs of China (Grant No. 20YFZCSY00310) and the Science Foundation of Tian** Health and Family Planning Commission of China (Grant Nos. 15KG114, TJWJ2022MS021 and 2010KY03).

Funding

The Funded was provided by the Key Project of Tian** Science and Technology Support Program of China (Grant No. 20YFZCSY00310) and the Science Foundation of Tian** Health and Family Planning Commission of China (Grant Nos. 15KG114, TJWJ2022MS021 and 2010KY03).

Author information

Author notes

  1. Yidan Wang and Zhenting Zhang have contributed equally to this study.

Authors and Affiliations

  1. Institute of Integrated Traditional Chinese and Western Medicine, Tian** University of Traditional Chinese Medicine, Tian**, 301617, China

    Yidan Wang

  2. Tian**’s Clinical Research Center for Cancer, Tian** Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tian**, 300060, China

    Zhenting Zhang

  3. Tian** Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tian** Third Central Hospital, Nankai University, Tian**, 300170, China

    Zhengyan Zhu, Peng Wang, **juan Zhang & Hui Liu

  4. Department of Pharmacy, Logistics University of Chinese People’s Armed Police Forces, Tian**, 300309, China

    Jianyu Li

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  1. Yidan Wang
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Contributions

HL and JL conceived and designed the study and all the experiments. YW, ZZ and HL performed the experiments and collected all data. ZZ, PW and JZ analyzed the data. HL and JL wrote and edited the manuscript. All authors read and approved the final manuscript.

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Correspondence to Hui Liu or Jianyu Li.

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Wang, Y., Zhang, Z., Zhu, Z. et al. The significance of EphA2-regulated Wnt/β-catenin signal pathway in promoting the metastasis of HBV-related hepatocellular carcinoma. Mol Biol Rep 50, 565–575 (2023). https://doi.org/10.1007/s11033-022-08045-1

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