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Endoplasmic reticulum stress regulates apoptosis and chemotherapeutic via enhancing TNFRSF10B recycling to the cell membrane in triple-negative breast cancer

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Abstract

Background

Triple-negative breast cancer (TNBC) is the most common malignant tumor in China. The expression and cell surface levels of TNF receptor superfamily member 10B (TNFRSF10B) are associated with apoptosis and chemotherapy. However, the precise molecular mechanisms that govern the regulation of TNFRSF10B remain unclear.

Materials and methods

RNA-Seq data related to TNBC chemotherapy resistance were acquired from the GEO database. The mRNA and protein levels of TNFRSF10B were detected using RT-PCR and Western blotting, respectively. Cell Counting Kit-8 (CCK-8) and colony formation assays were used to detect cell proliferation. Annexin V/7-AAD staining was used to evaluate apoptosis. The cell membrane TNFRSF10B was analyzed by Western blotting and immunofluorescence. Inducers and inhibitors of endoplasmic reticulum stress (ERS) were used to assess the effect of ERS on TNFRSF10B localization.

Results

TNFRSF10B expression was downregulated in TNBC and was associated with prognosis. TNFRSF10B overexpression inhibits the growth of TNBC both in vivo and in vitro and can partially counteract chemotherapy resistance. ERS activation in TNBC promotes the expression of TNFRSF10B, leading to its enrichment on the cell membrane surface, thereby activating the apoptotic pathways.

Conclusion

ERS regulates the expression and subcellular localization of TNFRSF10B in TNBC cells. They synergistically affect anti-apoptosis and chemotherapy resistance in TNBC cells.

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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

We thank Home for Researchers editorial team (www.home-for-researchers.com) for language editing service.

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Authors and Affiliations

  1. Breast Surgery (4Th General) Unit, General Surgery Department, General Hospital of Fushun Mining Bureau of Liaoning Health Industry, No.24 Centre Street, Xinfu District, Fushun City, 113008, Liaoning Province, China

    Dapeng Zhao, Jian Song & Chongyao Ji

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  1. Dapeng Zhao
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Contributions

Dapeng Zhao performed most experiments and drafted the manuscript; Jian Song analyzed the data; Chongyao Ji assisted in manuscript writing.

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Correspondence to Dapeng Zhao.

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The study was reviewed and approved by the Faculty of Science Ethics Committee at the General Hospital of Fushun Mining Bureau of Liaoning Health Industry.

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Zhao, D., Song, J. & Ji, C. Endoplasmic reticulum stress regulates apoptosis and chemotherapeutic via enhancing TNFRSF10B recycling to the cell membrane in triple-negative breast cancer. Clin Transl Oncol (2024). https://doi.org/10.1007/s12094-024-03509-1

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