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Tumor-promoting properties of enolase-phosphatase 1 in breast cancer via activating the NF-κB signaling pathway

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Abstract

Background

Evidence suggests that enolase-phosphatase 1 (ENOPH1) is involved in the progression of some certain types of cancers and acts as an oncogenic factor in tumor progression. The present study aimed to identify the central role of ENOPH1 in the progression of breast cancer (BC), a highly proliferative and aggressive disease.

Methods and results

ENOPH1 expression in BC tissues was explored based on the online resource and 40 paired fresh BC and para-carcinoma samples. Functional assays were performed to evaluate the biological effect of ENOPH1 on cell proliferation and migration in ENOPH1-silenced or overexpressing BC cell lines. Blockade of NF-κB by BAY11-7082 was performed to evaluate whether ENOPH1 exerted tumor-promoting properties via regulating the NF-κB signaling pathway. Results of the present study demonstrated that ENOPH1 expression was profoundly upregulated in BC tissues compared with adjacent breast tissues, and ENOPH1 expression was associated with cancer stage, node metastasis status, and overall survival. Functional assays demonstrated that ENOPH1 overexpression significantly accelerated BC cell proliferation, migration, and invasion, while genetic knockdown of ENOPH1 yielded the opposite effects. Mechanistically, ENOPH1 activated the NF-κB pathway, as evidenced by increased expression of NF-κB downstream genes and enhanced NF-κB p65 nuclear translocation. Furthermore, the oncogenic properties of ENOPH1 in proliferation, migration, and invasion were restrained following inhibition of the NF-κB signaling pathway.

Conclusions

These findings indicated the significance of ENOPH1 in promoting cell proliferation and invasion, mainly through activating the NF-κB pathway, suggesting that ENOPH1 might be an attractive prognostic factor and a potential target for BC therapy.

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Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

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Acknowledgements

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Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Author information

Authors and Affiliations

  1. Breast Center, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, Hebei, China

    Yuhui Bu & Li Ma

  2. Breast Center, Cangzhou People’s Hospital, Cangzhou, Hebei, China

    Yuhui Bu

  3. Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei, China

    Jun Hao

  4. Department of Breast Surgery, Affiliated Hospital of Hebei Engineering University, Handan, Hebei, China

    Jianchao He

  5. Department of Breast Surgery, The Fourth Hospital of Shijiazhuang, Shijiazhuang, Hebei, China

    Xiaolong Li

  6. Department of Breast Surgery, First Hospital of Qinhuangdao, Qinhuangdao, Hebei, China

    Yinfeng Liu

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  1. Yuhui Bu
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  4. Xiaolong Li
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Contributions

All authors contributed to the study conception and design. Yuhui Bu and Li Ma designed the study, analyzed the result and prepared the manuscripts. Jun Hao analyzed TCGA data, and performed experiment with Xiaolong Li and Jianchao He. Yinfeng Liu and Yuhui Bu were collected data and prepared the figures. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Li Ma.

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Conflict of interest

The authors declare that there is no conflict of interest regarding the publication of this article.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the Fourth Hospital of Hebei Medical University (approval No. 2020KY113). Informed consent was obtained from all individual participants included in the study.

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Bu, Y., Hao, J., He, J. et al. Tumor-promoting properties of enolase-phosphatase 1 in breast cancer via activating the NF-κB signaling pathway. Mol Biol Rep 50, 993–1004 (2023). https://doi.org/10.1007/s11033-022-08066-w

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