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ErbB2-upregulated HK1 and HK2 promote breast cancer cell proliferation, migration and invasion

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Abstract

ErbB2 is overexpressed in 15-20% of breast cancer, which is associated with malignancy and poor prognosis. We previously reported that ErbB2 supports malignant progression of breast cancer by upregulating lactate dehydrogenase A (LDHA), an important enzyme in glycolysis. However, whether ErbB2 promotes breast cancer progression through other glycolytic enzymes remains unclear. Hexokinase 1 (HK1) and hexokinase 2 (HK2) are the first rate-limiting enzymes of glycolysis and both of them are increased in breast cancer. Here, we aim to investigate whether ErbB2 upregulates HK1 and HK2 and the role of HK1 and HK2 in the malignant progression of ErbB2-overexpressing breast cancer. In current study, we found that the mRNA level of ErbB2 was positively correlated with that of HK1 and HK2, respectively. Moreover, ErbB2 upregulated the protein levels of HK1 and HK2 in breast cancer cells. We also found that both siHK1 and siHK2 significantly inhibited the proliferation, migration and invasion of ErbB2-overexpressing breast cancer cells. Taken together, our findings suggested that ErbB2 promoted the malignant progression of breast cancer cells by upregulating HK1 and HK2, and HK1 and HK2 might serve as promising therapeutic targets for ErbB2-overexpressing breast cancer.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81272907).

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Author notes

  1. Xuejiao Ma

    Present address: Department of Pharmacy, The First People’s Hospital of Kunming City, Kunming, 650500, China

Authors and Affiliations

  1. Department of Key Laboratory of Drug Targeting and Drug Delivery System of Ministry of Education, West China School of Pharmacy, Sichuan University, No. 17, Section 3, South Renmin Road, Chengdu, 610041, China

    Xuejiao Ma & Rong Yu

  2. Department of Biochemistry and Molecular Biology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, No. 17, Section 3, South Renmin Road, Chengdu, 610041, China

    Jingruo Chen, Bohan Huang, Shiqi Fu, Shuai Qu & Yuhua Zhao

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Contributions

Conceptualization: YZ and RY; Methodology: XM, JC and YZ; Formal analysis and investigation: XM, JC and BH; Writing-original draft preparation: XM; Writing-review and editing: XM, YZ, BH, SF and SQ; Funding acquisition: YZ; Supervision: YZ and RY. All authors have read and approved the final manuscript.

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Correspondence to Rong Yu or Yuhua Zhao.

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Ma, X., Chen, J., Huang, B. et al. ErbB2-upregulated HK1 and HK2 promote breast cancer cell proliferation, migration and invasion. Med Oncol 40, 154 (2023). https://doi.org/10.1007/s12032-023-02008-7

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