E2F1 promotes Warburg effect and cancer progression via upregulating ENO2 expression in Ewing sarcoma

Mol Med Rep. 2022 Jul;26(1):237. doi: 10.3892/mmr.2022.12753. Epub 2022 May 27.

Abstract

Altered glucose metabolism is an important characteristic of cancer cells, which is referred to as Warburg effect or aerobic glycolysis. Ewing sarcoma (EWS) is a highly malignant tumor that occurs in children and adolescents. However, the functions of aerobic glycolysis in EWS remain to be elucidated. The present study identified a transcription factor, E2F transcription factor 1 (E2F1), as a new regulator of cancer the aerobic glycolysis and progression in EWS. The present study showed that E2F1 modulated aerobic glycolysis in EWS cells by effecting glucose uptake, lactate production and ATP generation. Altered E2F1 expression increased or decreased cell viability and invasion in EWS. Mechanistically, the results demonstrated that E2F1 may promote the Warburg effect and cancer progression in EWS via upregulating enolase 2 expression. Generally, these findings indicated that E2F1 involvement in the progression of EWS and could serve as a clinical therapeutic target in EWS.

Keywords: E2F transcription factor 1; Ewing sarcoma; aerobic glycolysis; cancer progression.

MeSH terms

  • Adolescent
  • Cell Line, Tumor
  • Child
  • E2F1 Transcription Factor* / genetics
  • E2F1 Transcription Factor* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Phosphopyruvate Hydratase* / genetics
  • Phosphopyruvate Hydratase* / metabolism
  • Sarcoma, Ewing* / pathology
  • Transcription Factors / metabolism

Substances

  • E2F1 Transcription Factor
  • E2F1 protein, human
  • Transcription Factors
  • ENO2 protein, human
  • Phosphopyruvate Hydratase

Grants and funding

The present study was supported by the Joint Funds of Hubei Health Commission (grant no. WJ2019H362) and Medical Research Fund of Wu Han Commission (grant no. WX20Q21).