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

• Published in: Breast cancer research and treatment Vol. 189; no. 2; pp. 317 - 331
• Main Authors: Alfarsi, Lutfi H., El Ansari, Rokaya, Craze, Madeleine L., Mohammed, Omar J., Masisi, Brendah K., Ellis, Ian O., Rakha, Emad A., Green, Andrew R.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.09.2021; Springer; Springer Nature B.V
• Subjects: Amino Acid Transport System ASC - genetics; Amino acids; Analysis; Antineoplastic Agents, Hormonal - pharmacology; Antineoplastic Agents, Hormonal - therapeutic use; Biomarkers; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Cancer; Cancer research; Cell Line, Tumor; Drug Resistance, Neoplasm - genetics; Endocrine therapy; Estrogen; Estrogen receptors; Female; Gene Expression Regulation, Neoplastic; Genetic research; Health aspects; Humans; Medical colleges; Medicine; Medicine & Public Health; Metabolism; Minor Histocompatibility Antigens - genetics; Neoplasm Recurrence, Local; Oncology; Oncology, Experimental; Patients; Phenols; Preclinical Study; Prognosis; Proteomics; Receptors, Estrogen - genetics; Receptors, Estrogen - metabolism; Tamoxifen - therapeutic use; Therapeutic targets; Transaldolase - genetics; Tumors; TALDO1; Breast cancer; SLC1A5; Tamoxifen resistance; ER
• ISSN: 0167-6806; 1573-7217; 1573-7217
• DOI: 10.1007/s10549-021-06298-1

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.