The activation of asparagine synthetase by the transcription factor FOXM1 plays a pivotal role in the initiation and progression of ESCC

J Gene Med. 2024 Oct;26(10):e3741. doi: 10.1002/jgm.3741.

Abstract

This study explores the role of the transcription factor FOXM1 in the initiation and progression of oesophageal squamous cell carcinoma (ESCC). Our findings reveal that FOXM1 is highly expressed in ESCC and correlates with the prognosis of the disease. The relationship between FOXM1 and asparagine synthetase (ASNS) is investigated, and the study demonstrates that FOXM1 activates ASNS, impacting the tumour stemness of ESCC. In this study, we reveal the association between FOXM1 and ESCC development, as well as FOXM1's promotion of migration and proliferation in ESCC cells. The study also highlights FOXM1's regulation of ASNS transcription and the functional role of ASNS in ESCC metastasis and growth. Furthermore, the study explores the impact of FOXM1 and ASNS on ESCC stemness and their potential implications for chemotherapy resistance.

Keywords: ESCC; FOXM1; cancer stemness; transcription.

MeSH terms

  • Animals
  • Aspartate-Ammonia Ligase* / genetics
  • Aspartate-Ammonia Ligase* / metabolism
  • Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor
  • Cell Line, Tumor
  • Cell Movement* / genetics
  • Cell Proliferation* / genetics
  • Disease Progression*
  • Drug Resistance, Neoplasm / genetics
  • Esophageal Neoplasms* / genetics
  • Esophageal Neoplasms* / metabolism
  • Esophageal Neoplasms* / pathology
  • Esophageal Squamous Cell Carcinoma* / genetics
  • Esophageal Squamous Cell Carcinoma* / metabolism
  • Esophageal Squamous Cell Carcinoma* / pathology
  • Female
  • Forkhead Box Protein M1* / genetics
  • Forkhead Box Protein M1* / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mice
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Prognosis

Substances

  • Forkhead Box Protein M1
  • Aspartate-Ammonia Ligase
  • FOXM1 protein, human
  • ASNS protein, human
  • Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor