Abstract
Understanding the mechanisms underlying doxorubicin resistance in triple-negative breast cancer (TNBC) holds paramount clinical significance. In our study, we investigate the potential of STK32C, a little-explored kinase, to impact doxorubicin sensitivity in TNBC cells. Our findings reveal elevated STK32C expression in TNBC specimens, associated with unfavorable prognosis in doxorubicin-treated TNBC patients. Subsequent experiments highlighted that STK32C depletion significantly augmented the sensitivity of doxorubicin-resistant TNBC cells to doxorubicin. Mechanistically, we unveiled that the cytoplasmic subset of STK32C plays a pivotal role in mediating doxorubicin sensitivity, primarily through the regulation of glycolysis. Furthermore, the kinase activity of STK32C proved to be essential for its mediation of doxorubicin sensitivity, emphasizing its role as a kinase. Our study suggests that targeting STK32C may represent a novel therapeutic approach with the potential to improve doxorubicin’s efficacy in TNBC treatment.
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Data availability
Publicly available dataset analyzed in this study can be found here: TCGA (https://portal.gdc.cancer.gov/).
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Conceptualization: Huawei Xiao and Shaoyan Huang; Resources: Huawei Xiao, Lei Liu, and Shaoyan Huang; Data curation: Shaoyan Huang; Formal Analysis: Huawei Xiao, Lei Liu; Supervision: Shaoyan Huang; Validation: Huawei Xiao, Lei Liu; Investigation: Huawei Xiao, Lei Liu, and Shaoyan Huang; Visualization: Huawei Xiao; Methodology: Huawei Xiao and Lei Liu; Project administration: Shaoyan Huang; Writing – original draft: Huawei Xiao; Writing – review & editing: Huawei Xiao, Lei Liu, and Shaoyan Huang.
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Xiao, H., Liu, L. & Huang, S. STK32C modulates doxorubicin resistance in triple-negative breast cancer cells via glycolysis regulation. Mol Cell Biochem (2024). https://doi.org/10.1007/s11010-024-04989-z
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DOI: https://doi.org/10.1007/s11010-024-04989-z