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

Overview

Journal Pathobiology

Specialties Cell Biology
Pathology

Date 2024 Jun 11

PMID 38861938

Authors

Roshni Patel

Lutfi H Alfarsi

Rokaya El-Ansari

Brendah K Masisi

Busra Erkan

Ali Fakroun

Ian O Ellis

Emad A Rakha

Andrew R Green

Affiliations

Soon will be listed here.

Abstract

Introduction: ATF4, a stress-responsive transcription factor that upregulates adaptive genes, is a potential prognostic marker and modulator of glutamine metabolism in breast cancer. However, its exact role remains to be elucidated.

Methods: ATF4 expression was evaluated at genomic and transcriptomic levels using METABRIC (n = 1,980), GeneMiner (n = 4,712), and KM-Plotter datasets. Proteomic expression was assessed via immunohistochemistry (n = 2,225) in the Nottingham Primary Breast Cancer Series. ATF4 genomic copy number (CN) variation and mRNA/protein in association with clinicopathological parameters, amino acid transporters (AATs), and patient outcome were investigated.

Results: Genomic, transcriptomic, and proteomic overexpression of ATF4 was associated with more aggressive ER-negative tumours. ATF4 mRNA and protein expression were significantly associated with increased expression of glutamine related AATs including SLC1A5 (p < 0.01) and SLC7A11 (p < 0.02). High ATF4 and SLC1A5 protein expression was significantly associated with shorter breast cancer-specific survival (p < 0.01), especially in ER+ tumours (p < 0.01), while high ATF4 and SLC7A11 protein expression was associated with shorter survival (p < 0.01).

Conclusion: These findings suggest a complex interplay between ATF4 and AATs in breast cancer biology and underscore the potential role for ATF4 as a prognostic marker in ER+ breast cancer, offering a unique opportunity for risk stratification and personalized treatment strategies.

Citing Articles

SLC1A5 is a key regulator of glutamine metabolism and a prognostic marker for aggressive luminal breast cancer.

Alfarsi L, Ansari R, Erkan B, Fakroun A, Craze M, Aleskandarany M Sci Rep. 2025; 15(1):2805.

PMID: 39843491 PMC: 11754656. DOI: 10.1038/s41598-025-87292-1.

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