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B7 homolog 3 induces lung metastasis of breast cancer through Raf/MEK/ERK axis

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Abstract

Purpose

The essential action of B7 homolog 3 (B7-H3) in different diseases and cancers has been documented. We here focused on its role in breast cancer through the Raf/MEK/ERK axis regarding lung metastasis.

Methods

Expression pattern of B7-H3 was determined in breast cancer tissues and cells with its correlation with prognosis analyzed. Then, through transfection of lentivirus vector expressing B7-H3-shRNA, overexpression vector of B7-H3 (B7-H3-LV), U0126 (small molecule inhibitor of MEK), or PD98059 (small molecule inhibitor of ERK), the in vitro and in vivo effects of B7-H3 in breast cancer cell biological processes, and lung metastasis were analyzed in relation to the Raf/MEK/ERK axis.

Results

We discovered elevated B7-H3 in breast cancer and its elevation associated with poor prognosis. B7-H3 promoted the malignant properties of breast cancer cells, accompanied with increased N-cadherin and vimentin and reduced E-cadherin. Additionally, overexpression of B7-H3 accelerated the lung metastasis in breast cancer in vivo. All the above promoting action of B7-H3 was achieved through activation of the Raf/MEK/ERK signaling pathway.

Conclusion

Taken together, B7-H3 can promote lung metastasis in breast cancer through activation of the Raf/MEK/ERK axis.

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Data availability

The original contributions presented in the study are included in the article/supplementary material and further inquiries can be directed to the corresponding authors.

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Acknowledgements

This study was supported by General Project of Shandong Provincial Natural Science Foundation (ZR2020MH242; ZR2020MH293); Department of Health of Shandong Province (2018WS068).

Funding

This study was supported by General Project of Shandong Provincial Natural Science Foundation (ZR2020MH242; ZR2020MH293); Department of Health of Shandong Province (2018WS068).

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Author notes

  1. Shuai Wang and Xinyan Zhang are sharing co-first authorship.

Authors and Affiliations

  1. Department of Radiotherapy, Affiliated Hospital of Weifang Medical University, No. 2428, Yuhe Road, Weifang, 261031, Shandong Province, China

    Shuai Wang & Ruimei Sun

  2. School of Medical Imaging, Weifang Medical University, No. 7166, Baotong West Street, Weifang, 261053, Shandong Province, China

    Houfa Ning, Senyi Dong & Guangzhi Wang

  3. Department of Intervention, The Affiliated Weihai Second Municipal Hospital of Qingdao University, Weihai, 264200, China

    Xinyan Zhang

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  1. Shuai Wang
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  4. Senyi Dong
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Contributions

All authors designed the study. SD, GW, and RS collated the data, designed and developed the database, carried out data analyses, and produced the initial draft of the manuscript. SW, XZ, and HN contributed to drafting the manuscript. All authors have read and approved the final submitted manuscript.

Corresponding authors

Correspondence to Guangzhi Wang or Ruimei Sun.

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The authors declare that they have no conflict of interest.

Ethical approval

The present study was performed with the approval of the ethics committee of Affiliated Hospital of Weifang Medical University, with signed informed consent obtained from all participating individuals. The animal experiment was conducted following the guidelines for the care and use of laboratory animals issued by the National Institutes of Health.

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Wang, S., Zhang, X., Ning, H. et al. B7 homolog 3 induces lung metastasis of breast cancer through Raf/MEK/ERK axis. Breast Cancer Res Treat 193, 405–416 (2022). https://doi.org/10.1007/s10549-022-06520-8

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