Co-Expression Effect of SLC7A5/SLC3A2 to Predict Response to Endocrine Therapy in Oestrogen-Receptor-Positive Breast Cancer
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Updated: Dec 27, 2025
Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Lutfi H Alfarsi1, Rokaya El-Ansari1, Madeleine L Craze1
1Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK.
Abstract:
The majority of breast cancers are oestrogen-receptor-positive (ER+) and are subject to endocrine therapy; however, an unpredictable subgroup of patients will develop resistance to endocrine therapy. The SLC7A5/SLC3A2 complex is a major route for the transport of large neutral essential amino acids through the plasma membrane. Alterations in the expression and function of those amino-acid transporters lead to metabolic reprogramming, which contributes to the tumorigenesis and drug resistance. This study aims to assess the effects and roles of SLC7A5/SLC3A2 co-expression in predicting responses to endocrine therapy in patients with ER+ breast cancer. The biological and clinical impact of SLC7A5/SLC3A2 co-expression was assessed in large annotated cohorts of ER+/HER2- breast cancer with long-term follow-up at the mRNA and protein levels. In vitro experiments were conducted to investigate the effect of SLC7A5/SLC3A2 knockdown in the proliferation of cancer cells and to the sensitivity to tamoxifen. We found that proliferation-related genes are highly expressed in a subgroup of patients with high SLC7A5/SLC3A2, and knockdown of SLC7A5/SLC3A2 decreased proliferation of ER+ breast cancer cells. In patients treated with endocrine therapy, high SLC7A5/SLC3A2 co-expression was associated with poor patient outcome, and depletion of SLC7A5/SLC3A2 using siRNA increased the sensitivity of breast cancer cells to tamoxifen. On the basis of our findings, SLC7A5/SLC3A2 co-expression has the potential of identifying a subgroup of ER+/HER2- breast cancer patients who fail to benefit from endocrine therapy and could guide the choice of other alternative therapies.
Insights
High co-expression of SLC7A5/SLC3A2 amino acid transporters predicts poor response to endocrine therapy in oestrogen-receptor-positive breast cancer. Targeting SLC7A5/SLC3A2 may improve treatment outcomes for these patients.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Oestrogen-receptor-positive (ER+) breast cancer often relies on endocrine therapy.
- A subset of ER+ breast cancer patients develop resistance to endocrine therapy, necessitating alternative treatment strategies.
- The SLC7A5/SLC3A2 amino acid transporter complex is implicated in metabolic reprogramming, contributing to cancer progression and drug resistance.
Purpose of the Study:
- To investigate the role of SLC7A5/SLC3A2 co-expression in predicting endocrine therapy response in ER+ breast cancer.
- To assess the biological and clinical impact of SLC7A5/SLC3A2 co-expression on patient outcomes.
- To explore the therapeutic potential of targeting SLC7A5/SLC3A2 in endocrine-resistant breast cancer.
Main Methods:
- Analysis of SLC7A5/SLC3A2 co-expression at mRNA and protein levels in large ER+/HER2- breast cancer cohorts.
- In vitro studies involving SLC7A5/SLC3A2 knockdown using siRNA to assess effects on cancer cell proliferation and tamoxifen sensitivity.
- Correlation of SLC7A5/SLC3A2 expression with clinical outcomes in patients receiving endocrine therapy.
Main Results:
- High SLC7A5/SLC3A2 co-expression was associated with increased expression of proliferation-related genes.
- Knockdown of SLC7A5/SLC3A2 reduced proliferation in ER+ breast cancer cells.
- Elevated SLC7A5/SLC3A2 co-expression correlated with poor outcomes in patients treated with endocrine therapy.
- Depletion of SLC7A5/SLC3A2 enhanced breast cancer cell sensitivity to tamoxifen.
Conclusions:
- SLC7A5/SLC3A2 co-expression serves as a potential biomarker for identifying ER+/HER2- breast cancer patients unlikely to benefit from endocrine therapy.
- Targeting the SLC7A5/SLC3A2 complex may offer a viable therapeutic strategy for overcoming endocrine resistance in breast cancer.
- These findings could guide the selection of alternative therapies for patients with high SLC7A5/SLC3A2 expression.
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