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ATF4 as a Prognostic Marker and Modulator of Glutamine Metabolism in Oestrogen Receptor-Positive Breast Cancer

  • 0Nottingham Breast Cancer Research Centre, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham, UK.
Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology +

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June 11, 2024

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June 11, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Activating transcription factor 4 (ATF4) is linked to aggressive breast cancer and altered glutamine metabolism. Its expression correlates with amino acid transporters and impacts patient survival, especially in ER+ tumors.

Area Of Science

  • Oncology
  • Molecular Biology
  • Cancer Metabolism

Background

  • Activating transcription factor 4 (ATF4) is a stress-responsive transcription factor.
  • ATF4 influences adaptive gene expression and glutamine metabolism in breast cancer.
  • Its precise role and prognostic value in breast cancer require further investigation.

Purpose Of The Study

  • To elucidate the role of ATF4 in breast cancer.
  • To investigate the association between ATF4 expression and glutamine metabolism.
  • To evaluate ATF4 as a prognostic marker in breast cancer.

Main Methods

  • ATF4 expression was analyzed at genomic, transcriptomic, and proteomic levels using large patient datasets (METABRIC, GeneMiner, KM-Plotter, Nottingham Breast Cancer Series).
  • Genomic copy number variation, mRNA, and protein levels were assessed.
  • Associations with clinicopathological parameters, amino acid transporters (AATs), and patient survival were investigated.

Main Results

  • Overexpression of ATF4 (genomic, transcriptomic, proteomic) correlated with aggressive ER-negative breast tumors.
  • ATF4 expression was significantly linked to increased expression of glutamine transporters SLC1A5 and SLC7A11.
  • High ATF4 and SLC1A5/SLC7A11 protein levels were associated with shorter breast cancer-specific survival, particularly in ER+ tumors.

Conclusions

  • ATF4 interacts complexly with amino acid transporters in breast cancer.
  • ATF4 shows potential as a prognostic marker for ER+ breast cancer.
  • These findings support ATF4's utility in risk stratification and personalized treatment strategies.

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