SLC1A5 co-expression with TALDO1 associates with endocrine therapy failure in estrogen receptor-positive breast cancer
| Autor: | Emad A. Rakha, Andrew R. Green, Lutfi Alfarsi, Ian O. Ellis, Madeleine L. Craze, Omar J. Mohammed, Rokaya El Ansari, Brendah K. Masisi |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Amino Acid Transport System ASC Proteomics Cancer Research Antineoplastic Agents Hormonal SLC1A5 Estrogen receptor Breast Neoplasms Transcriptome Minor Histocompatibility Antigens 03 medical and health sciences 0302 clinical medicine Breast cancer Preclinical Study Cell Line Tumor TALDO1 medicine Endocrine system Humans Gene knockdown Predictive marker business.industry Cancer Tamoxifen resistance medicine.disease Transaldolase Gene Expression Regulation Neoplastic Tamoxifen 030104 developmental biology Oncology Receptors Estrogen ER Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer research Female Neoplasm Recurrence Local business medicine.drug |
| Zdroj: | Breast Cancer Research and Treatment |
| ISSN: | 1573-7217 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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