ELF4 contributes to esophageal squamous cell carcinoma growth and metastasis by augmenting cancer stemness via FUT9

Acta Biochim Biophys Sin (Shanghai). 2024 Jan 25;56(1):129-139. doi: 10.3724/abbs.2023225.

Abstract

Esophageal squamous cell carcinoma (ESCC) commonly has aggressive properties and a poor prognosis. Investigating the molecular mechanisms underlying the progression of ESCC is crucial for developing effective therapeutic strategies. Here, by performing transcriptome sequencing in ESCC and adjacent normal tissues, we find that E74-like transcription factor 4 (ELF4) is the main upregulated transcription factor in ESCC. The results of the immunohistochemistry show that ELF4 is overexpressed in ESCC tissues and is significantly correlated with cancer staging and prognosis. Furthermore, we demonstrate that ELF4 could promote cancer cell proliferation, migration, invasion, and stemness by in vivo assays. Through RNA-seq and ChIP assays, we find that the stemness-related gene fucosyltransferase 9 ( FUT9) is transcriptionally activated by ELF4. Meanwhile, ELF4 is verified to affect ESCC cancer stemness by regulating FUT9 expression. Overall, we first discover that the transcription factor ELF4 is overexpressed in ESCC and can promote ESCC progression by transcriptionally upregulating the stemness-related gene FUT9.

Keywords: ELF4; FUT9; esophageal squamous cell carcinoma; stemness; transcription factor.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Esophageal Neoplasms* / metabolism
  • Esophageal Squamous Cell Carcinoma* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Transcription Factors
  • ELF4 protein, human
  • DNA-Binding Proteins

Grants and funding

This work was supported by the grants from the National Natural Science Foundation of China (Nos. 82072684 and 82073224), the Shanghai Committee of Science and Technology (Nos. 20XD1402900, 21XD1423100, 21JC1405200 and 18140900100), and the Medical Discipline Construction Project of Pudong Health Committee of Shanghai (Nos. PWZxq2022-6 and PWYgf2021-2).