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SLC38A5 promotes glutamine metabolism and inhibits cisplatin chemosensitivity in breast cancer

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Abstract

Background

Solute carrier family 38 member 5 (SLC38A5), as an amino acid transporter, play a vital role in cellular biological processes. In this study, we analyzed the function of SLC38A5 and its potential mechanism in breast cancer (BC) progression.

Methods

The expression of SLC38A5 in cancer and adjacent-normal tissues was analyzed by qRT-PCR and Western blot, and its correlation with patient prognosis was analyzed. The immunohistochemical staining of cancer tissues and adjacent-normal tissues was performed on SLC38A5-positive specimens. BC mice were successfully applied to examine the role of SLC38A5 on tumor proliferation using the CCK-8 assay. In BC cells and mouse tumor tissues, SLC38A5 and PCNA expression were determined by Western blotting.

Results

The study found that SLC38A5 was highly expressed in BC patients and associated with a poor survival. SLC38A5 silencing inhibited BC cell viability and glutamine uptake. In addition, SLC38A5 overexpression promoted BC cell viability via the glutamine metabolism. SLC38A5 inhibited cisplatin chemosensitivity in BC cells. Importantly, SLC38A5 silencing inhibited tumor growth in vivo.

Conclusion

Our findings suggest that SLC38A5 enhances BC cell viability by glutamine metabolism, inhibits the chemical sensitivity of cisplatin in BC cells, and promotes tumor growth, emphasizing the clinical relevance of SLC38A5 in BC management as a novel potential therapeutic target.

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Availability of data and materials

The data that support the findings of this study are available on request from the corresponding author.

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Funding

This study was funded by Shanghai Natural Science Foundation (20ZR1411900) and Shanghai Health Care Commission (202040065).

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Author notes

  1. Xiaowei Shen, Ganggang Wang, and Hua He have contributed equally to this work.

Authors and Affiliations

  1. Department of General Surgery, QingPu Branch of Zhongshan Hospital Affiliated to Fudan University, QingPu District Central Hospital Shanghai, No. 1158, Gong Yuan Dong Road, Shanghai, 201700, China

    Xiaowei Shen, Hua He, Ping Shang, Bin Yan, Xiaoliang Wang & Weixing Shen

  2. Department of Hepatobiliary Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China

    Ganggang Wang & Xiaoliang Wang

Authors
  1. Xiaowei Shen
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  2. Ganggang Wang
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  4. Ping Shang
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  5. Bin Yan
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  6. Xiaoliang Wang
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Contributions

Xiaowei Shen, Ganggang Wang, and Hua He wrote the paper and conceived and designed the experiments; Xiaowei Shen, and Ganggang Wang analyzed the data; Ping Shang, Bin Yan, Xiaoliang Wang, and Weixing Shen collected and provided the sample for this study. All the authors have read and approved the final submitted manuscript.

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Correspondence to Xiaowei Shen.

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Shen, X., Wang, G., He, H. et al. SLC38A5 promotes glutamine metabolism and inhibits cisplatin chemosensitivity in breast cancer. Breast Cancer 31, 96–104 (2024). https://doi.org/10.1007/s12282-023-01516-8

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  • DOI: https://doi.org/10.1007/s12282-023-01516-8

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