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

Med Oncol. 2022 Jan 29;39(4):45. doi: 10.1007/s12032-021-01641-4.

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.

Keywords: Breast cancer; ErbB2; Glycolysis; HSF1/LDHA axis; Migration and invasion.

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Glucose / metabolism
  • Glycolysis / drug effects
  • Glycolysis / genetics*
  • Heat Shock Transcription Factors / genetics
  • Heat Shock Transcription Factors / metabolism*
  • Humans
  • L-Lactate Dehydrogenase / genetics
  • L-Lactate Dehydrogenase / metabolism*
  • Neoplasm Metastasis
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism*

Substances

  • HSF1 protein, human
  • Heat Shock Transcription Factors
  • L-Lactate Dehydrogenase
  • LDHA protein, human
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Glucose