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SLC1A5 co-expression with TALDO1 associates with endocrine therapy failure in oestrogen receptor-positive breast cancer

Alfarsi, Lutfi H.; Ansari, Rokaya El; Craze, Madeleine L.; Mohammed, Omar J.; Masisi, Brendah K.; Ellis, Ian O.; Rakha, Emad A.; Green, Andrew R.


Lutfi H. Alfarsi

Rokaya El Ansari

Madeleine L. Craze

Omar J. Mohammed

Brendah K. Masisi

Professor of Breast Cancer Pathology


Purpose: Identification of effective biomarkers for the benefit of endocrine treatment and understanding the molecular pathways that contribute to the development of resistance are of crucial importance to the management of luminal breast cancer. The amino acid transporter SLC1A5 has emerging importance as a prognostic marker and potential therapeutic target in various types of cancer. This study aims to investigate its role in luminal breast cancer as a potential predictive marker for endocrine treatment.
Methods: SLC1A5 expression was assessed at the transcriptomic and proteomic levels in large, well-characterized cohorts of luminal breast cancer. The sensitivity to endocrine therapy after SLC1A5 knockdown was investigated in vitro, using MCF7 and MDA-MB-175 cell lines. Bioinformatic analyses were performed to study the interacting networks of SLC1A5, and to identify a key co-expressed gene with SLC1A5.
Results: here we showed that patients with tumors that highly expressed SLC1A5 associated with a high risk of relapse after endocrine treatment. In vitro, depletion of SLC1A5 increases the sensitivity of luminal breast cancer cells to tamoxifen. TALDO1 was identified as key co-expressed gene with SLC1A5, and in vitro knockdown of SLC1A5 showed reduction in TALDO1 expression. Indeed, TALDO1 was associated with poor clinical outcomes in patients who were subject to endocrine therapy.
Conclusion: These findings suggest that metabolic alterations, particularly the interaction between the key amino acid transporter SLC1A5 and metabolic enzyme TALDO1, could affect the sensitivity of endocrine therapy. This study demonstrated the prognostic value of both SLC1A5 and TALDO1 as biomarkers in luminal breast cancer.


Alfarsi, L. H., Ansari, R. E., Craze, M. L., Mohammed, O. J., Masisi, B. K., Ellis, I. O., …Green, A. R. (2021). SLC1A5 co-expression with TALDO1 associates with endocrine therapy failure in oestrogen receptor-positive breast cancer. Breast Cancer Research and Treatment, 189(2), 317-331.

Journal Article Type Article
Acceptance Date Jun 12, 2021
Online Publication Date Jul 19, 2021
Publication Date 2021-09
Deposit Date Jun 22, 2021
Publicly Available Date Jul 20, 2022
Journal Breast Cancer Research and Treatment
Print ISSN 0167-6806
Electronic ISSN 1573-7217
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Volume 189
Issue 2
Pages 317-331
Public URL
Publisher URL


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