ArticleBreast cancer research : BCR2022
Selective pressure of endocrine therapy activates the integrated stress response through NFκB signaling in a subpopulation of ER positive breast cancer cells.
Article in Breast cancer research : BCR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- Integrative pipeline to profile and target endocrine therapy-insensitive cell populations in ER+ breast cancer.bioRxiv : the preprint server for biology · 2026Article
- Article
- Estrogen Receptor Alpha Mutations, Truncations, Heterodimers, and Therapies.Endocrinology · 2024Review
- Anti-cancer potential of substituted "amino-alkyl-rhodamine" derivatives against MCF-7 human breast cancer cell line.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Cysteine dioxygenase 1 attenuates the proliferation via inducing oxidative stress and integrated stress response in gastric cancer cells.Cell death discovery · 2022Article
- Identification of a novel ER-NFĸB-driven stem-like cell population associated with relapse of ER+ breast tumors.Breast cancer research : BCR · 2022Article
- Relationship of micro-RNA, mRNA and eIF Expression in Tamoxifen-Adapted MCF-7 Breast Cancer Cells: Impact of miR-1972 on Gene Expression, Proliferation and Migration.Biomolecules · 2022Article
- Article
- HighCancer diagnosis & prognosisArticle
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundWhile estrogen receptor (ER) positive breast tumors generally respond well to endocrine therapy (ET), up to 40% of patients will experience relapse, either while on endocrine therapy or after ET is completed. We previously demonstrated that the selective pressure of tamoxifen activates the NFκB pathway in ER + patient tumors, breast cancer cell lines, and breast cancer xenograft tumors, and that this activation allows for survival of a subpopulation of NFκB + cells that contribute to cell regrowth and tumor relapse after ET withdrawal. However, the mechanisms contributing to the expansion of an NFκB + cell population on ET are unknown.
methodsHere, we utilized single-cell RNA sequencing and bioinformatics approaches to characterize the NFκB + cell population and its clinical relevance. Follow-up studies were conducted to validate our findings and assess the function of the integrated stress response pathway in breast cancer cell lines and patient-derived models.
resultsWe found that the NFκB + population that arises in response to ET is a preexisting population is enriched under the selective pressure of ET. Based on the preexisting NFκB + cell population, we developed a gene signature and found that it is predictive of tumor relapse when expressed in primary ER + tumors and is retained in metastatic cell populations. Moreover, we identified that the integrated stress response (ISR), as indicated by increased phosphorylation of eIF2α, occurs in response to ET and contributes to clonogenic growth under the selective pressure of ET.
conclusionsTaken together, our findings suggest that a cell population with active NFκB and ISR signaling can survive and expand under the selective pressure of ET and that targeting this population may be a viable therapeutic strategy to improve patient outcome by eliminating cells that survive ET. Understanding the mechanisms by which breast cancer cells survive the selective pressure of ET may improve relapse rates and overall outcome for patients with ER + breast tumors.
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