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ST8SIA1 inhibition sensitizes triple negative breast cancer to chemotherapy via suppressing Wnt/β-catenin and FAK/Akt/mTOR

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Abstract

Background

Chemoresistance is the major cause of therapeutic failure in triple negative breast cancer (TNBC). In this work, we investigated the molecular mechanism for the development of TNBC chemoresistance.

Methods

mRNA and protein levels of ST8SIA1 were analyzed in chemosensitive and chemoresistant TNBC cells and tissues. Proliferation and survival assays were performed to determine the role of ST8SIA1 in TNBC chemoresistance.

Results

We found that ST8SIA1 mRNA and protein levels were increased in multiple TNBC cell lines after prolonged exposure to chemotherapeutic drugs. Consistently, retrospective study demonstrated that the majority of TNBC patients who developed chemoresistance displayed upregulation of ST8SIA1. We further found that chemoresistant TNBC cells were more sensitive than chemosensitive cells to ST8SIA1 inhibition in decreasing growth and viability. Consistently, ST8SIA1 inhibition augmented the efficacy of chemotherapy in TNBC cells. Mechanism studies demonstrated that ST8SIA1 inhibition led to suppression of FAK/Akt/mTOR and Wnt/β-catenin signalling pathways.

Conclusions

These findings provide an explanation for the heterogeneity of chemotherapy responses across TNBC individuals and reveal the supportive roles of ST8SIA1in TNBC chemoresistance.

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Acknowledgements

The authors acknowledge the staff of the Department of Oncology, Sanya People’s Hospital and Hannan People’s Hospital for their assistance with patient samples. This work was supported by Hainan Provincial Natural Science Foundation of China (Grant no. 814315).

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Authors and Affiliations

  1. Department of Oncology, Sanya People’s Hospital, Sanya, 572000, China

    H. Wan & Z. Li

  2. Department of Pathology, Sanya People’s Hospital, Sanya, 572000, China

    H. Wang

  3. Department of Pharmacy, Sanya People’s Hospital, Sanya, 572000, China

    F. Cai

  4. Department of Oncology, Hainan General Hospital, No.19, Xinhua Road, Xiuying District, Haikou, 570311, Hainan, China

    L. Wang

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  1. H. Wan
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  5. L. Wang
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Contributions

HXW and LW designed the experiments, interpreted the data and wrote the manuscript. ZQL, HW and FC performed the experiments. All authors approved the final manuscripts.

Corresponding author

Correspondence to L. Wang.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Wan, H., Li, Z., Wang, H. et al. ST8SIA1 inhibition sensitizes triple negative breast cancer to chemotherapy via suppressing Wnt/β-catenin and FAK/Akt/mTOR. Clin Transl Oncol 23, 902–910 (2021). https://doi.org/10.1007/s12094-020-02484-7

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  • DOI: https://doi.org/10.1007/s12094-020-02484-7

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