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BMX activates Wnt/β-catenin signaling pathway to promote cell proliferation and migration in breast cancer

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Abstract

Background

Breast cancer has become a dangerous killer for the female, which seriously threatened women's life, leading to huge pressures to society. The present study assessed the mechanism underlying the involvement of bone marrow tyrosine kinase on chromosome X (BMX) in breast cancer development.

Methods

The expression of BMX was examined by qPCR and immunohistochemistry. The effect of BMX on cell proliferation and migration was detected by Clone formation assay and Transwell assay. In vitro study, the correlation of BMX with Wnt/β-catenin pathway was explored by western blot and TOP/FOP flash assay.

Results

In the present study, we found that BMX was up-regulated in breast cancer, which was associated with the tumor differentiation and TNM stage. Oncogenic BMX enhanced the ability of breast cancer cell proliferation and migration. Furthermore, BMX could up-regulate the protein expression levels of p-β-catenin (Y142), p-β-catenin(Y654) and inhibit the expression level of p-β-catenin (S33/37), thus activating Wnt/β-catenin pathway in MCF-7 and MDA-MB-231 cells. In addition, we revealed that BMX promoted GSK3β phosphorylation, which suppressed the degradation of β-catenin.

Conclusions

In this study, we identified that BMX-activated Wnt/β-catenin signaling pathway, playing an oncogenic role in breast cancer, suggesting that BMX could become a potential treatment target of breast cancer.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81472765) and the Key Project of Science and Technology Department of Hubei Province (2015CFA070).

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Author notes

  1. Kai Li, Wen-ting Pan and Yan-bin Ma Contributed equally.

Authors and Affiliations

  1. Department of Breast and Thyroid Surgery, Zhongnan Hospital, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan University, 169 Donghu Road, Wuchang District, Wuhan, 430071, Hubei, China

    Jing-wei Zhang

  2. Department of Pathology and Pathophysiology, Hubei Provincial Key Laboratory of Developmentally Originated Disease, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, Hubei, China

    Kai Li, Wen-ting Pan, Yan-bin Ma, Xiao-long Xu, Yang Gao, Yan-qi He & Lei Wei

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  1. Kai Li
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Correspondence to Jing-wei Zhang.

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Li, K., Pan, Wt., Ma, Yb. et al. BMX activates Wnt/β-catenin signaling pathway to promote cell proliferation and migration in breast cancer. Breast Cancer 27, 363–371 (2020). https://doi.org/10.1007/s12282-019-01024-8

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  • DOI: https://doi.org/10.1007/s12282-019-01024-8

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