ATF4 as a Prognostic Marker and Modulator of Glutamine Metabolism in Oestrogen Receptor-Positive Breast Cancer
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.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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ATF4 as a Prognostic Marker and Modulator of Glutamine Metabolism in Oestrogen Receptor-Positive Breast Cancer ; volume:91 ; number:6 ; year:2024 ; pages:411-421 ; extent:11
Pathobiology ; 91, Heft 6 (2024), 411-421 (gesamt 11)
- Creator
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Patel, Roshni
Alfarsi, Lutfi H.
El-Ansari, Rokaya
Masisi, Brendah K.
Erkan, Busra
Fakroun, Ali
Ellis, Ian O.
Rakha, Emad A.
Green, Andrew R.
- DOI
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10.1159/000539564
- URN
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urn:nbn:de:101:1-2412112338008.437751545695
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:33 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Patel, Roshni
- Alfarsi, Lutfi H.
- El-Ansari, Rokaya
- Masisi, Brendah K.
- Erkan, Busra
- Fakroun, Ali
- Ellis, Ian O.
- Rakha, Emad A.
- Green, Andrew R.
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Oestrogen deprivation induces chemokine production and immune cell recruitment in in vitro and in vivo models of oestrogen receptor-positive breast cancer
Glutamine metabolism, the Achilles heel for medulloblastoma tumor
PGC-1α supports glutamine metabolism in breast cancer
Targeting glutamine metabolism slows soft tissue sarcoma growth
Molecular changes in premenopausal oestrogen receptor-positive primary breast cancer in Vietnamese women after oophorectomy
Clinical and molecular predictors of very late recurrence in oestrogen receptor-positive breast cancer patients
Implications of obesity and insulin resistance for the treatment of oestrogen receptor-positive breast cancer
Inhibition of glutamine uptake regulates mTORC1, glutamine metabolism and cell growth in prostate cancer
Glutamine metabolism in mammalian tissues
Zinc Modulates Glutamine Metabolism in T Cells
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Oestrogen deprivation induces chemokine production and immune cell recruitment in in vitro and in vivo models of oestrogen receptor-positive breast cancer
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PGC-1α supports glutamine metabolism in breast cancer
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