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ErbB2 promotes breast cancer metastatic potential via HSF1/LDHA axis-mediated glycolysis

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Abstract

ErbB2 is overexpressed in approximately 25% of breast cancer cases and promotes metastatic potential. We previously reported that ErbB2 promoted glycolysis via heat shock factor 1 (HSF1)/lactate dehydrogenase A (LDHA) axis and ErbB2-mediated glycolysis was required for the growth of breast cancer cells. However, the importance of HSF1/LDHA axis-mediated glycolysis in ErbB2-enhanced metastatic potential remains to be elucidated. In this study, we investigated the effect of HSF1/LDHA axis-mediated glycolysis on migration and invasion in breast cancer cells. Firstly, we demonstrated that ErbB2-mediated migration and invasion were dependent on glycolysis in breast cancer cells. Secondly, we found that HSF1/LDHA axis played an important role in glycolysis, which contributed to ErbB2-enhanced migration and invasion. Finally, we showed that ErbB2 was positively correlated with HSF1/LDHA axis in invasive breast cancer patients via GEO analysis. Taken together, ErbB2 promoted metastatic potential of breast cancer cells via HSF1/LDHA axis-mediated glycolysis. And our findings indicated that targeting HSF1/LDHA axis may be a promising strategy to treat ErbB2-overexpressing breast cancer patients.

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Acknowledgements

We thank Prof. Ming Shi (Institute of Basic Medical Sciences, Beijing, China) for providing MCF7/ErbB2 cell line. We thank Dr. Guan Wang (State Key Laboratory of Biotherapy, Sichuan University, China) for assistance with GEO analysis. We thank Kelly Smith (Mitchell Cancer Institute, University of South Alabama, USA) for polishing this paper.

Funding

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

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Author notes

  1. Sufang Jiang

    Present address: Department of Anesthesiology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, China

  2. Li He and Sinan Lv have contributed equally to this work.

Authors and Affiliations

  1. 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

    Li He, Sinan Lv, Xuejiao Ma, Sufang Jiang, Fang Zhou, Yunwu Zhang & Yuhua Zhao

  2. 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

    Li He, Xuejiao Ma & Rong Yu

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  1. Li He
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Contributions

Conceptualization: YZ and RY; Methodology: LH, SL, and YZ; Formal analysis and investigation: LH, SL, XM, and SJ; FZ; Writing-original draft preparation: LH; Writing-review and editing: YZ and SL; Funding acquisition: YZ; Resources: 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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He, L., Lv, S., Ma, X. et al. ErbB2 promotes breast cancer metastatic potential via HSF1/LDHA axis-mediated glycolysis. Med Oncol 39, 45 (2022). https://doi.org/10.1007/s12032-021-01641-4

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