Identification of a novel ER-NF?B-driven stem-like cell population associated with relapse of ER+?breast tumors. Journal Article

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Authors: Semina, SE; Alejo, LH; Chopra, S; Kansara, NS; Kastrati, I; Sartorius, CA; Frasor, J
Article Title: Identification of a novel ER-NF?B-driven stem-like cell population associated with relapse of ER+?breast tumors.
Abstract: BACKGROUND: Up to 40% of patients with estrogen receptor-positive (ER+) breast cancer experience relapse. This can be attributed to breast cancer stem cells (BCSCs), which are known to be involved in therapy resistance, relapse, and metastasis. Therefore, there is an urgent need to identify genes/pathways that drive stem-like cell properties in ER+ breast tumors. METHODS: Using single-cell RNA sequencing and various bioinformatics approaches, we identified a unique stem-like population and established its clinical relevance. With follow-up studies, we validated our bioinformatics findings and confirmed the role of ER and NF?B in the promotion of stem-like properties in breast cancer cell lines and patient-derived models. RESULTS: We identified a novel quiescent stem-like cell population that is driven by ER and NF?B in multiple ER+ breast cancer models. Moreover, we found that a gene signature derived from this stem-like population is expressed in primary ER+ breast tumors, endocrine therapy-resistant and metastatic cell populations and predictive of poor patient outcome. CONCLUSIONS: These findings indicate a novel role for ER and NF?B crosstalk in BCSCs biology and understanding the mechanism by which these pathways promote stem properties can be exploited to improve outcomes for ER+ breast cancer patients at risk of relapse.
Journal Title: Breast cancer research : BCR
Publisher: Unknown  
Date Published: 2022