ArticleAging2018
The ER-alpha mutation Y537S confers Tamoxifen-resistance via enhanced mitochondrial metabolism, glycolysis and Rho-GDI/PTEN signaling: Implicating TIGAR in somatic resistance to endocrine therapy.
Article in Aging, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Discovery of ERα-Targeting Phytochemicals With In Vitro Cytotoxicity and Computational Prediction of Y537S Mutant Inhibition.Chemical biology & drug design · 2026Article
- Harnessing the novel safeguarding role of Selenoprotein T in age-related myocardial left and right decline through the ferroptosis-mitochondrial axis.Journal of translational medicine · 2026Article
- Androgen Receptors Promote Oxidative Phosphorylation and Resistance to Palmitate Lipotoxicity in ER-Mutant Breast Cancer.Endocrinology · 2025Article
- High mitochondrial DNA content is a key determinant of stemness, proliferation, cell migration, and cancer metastasis in vivo.Cell death & disease · 2024Article
- Novel CD44-Targeted Albumin Nanoparticles: An Innovative Approach to Improve Breast Cancer Treatment.International journal of molecular sciences · 2024Article
- Modulating Glycolysis to Improve Cancer Therapy.International journal of molecular sciences · 2023Review
- Article
- Resistance to endocrine therapy in HR + and/or HER2 + breast cancer: the most promising predictive biomarkers.Molecular biology reports · 2022Review
- MLL3 is a de novo cause of endocrine therapy resistance.Cancer medicine · 2021Article
- Fatty acid oxidation and autophagy promote endoxifen resistance and counter the effect of AKT inhibition in ER-positive breast cancer cells.Journal of molecular cell biology · 2021Article
- Estrogen Receptor Alpha Mutations in Breast Cancer Cells Cause Gene Expression Changes through Constant Activity and Secondary Effects.Cancer research · 2021Article
- High ATP Production Fuels Cancer Drug Resistance and Metastasis: Implications for Mitochondrial ATP Depletion Therapy.Frontiers in oncology · 2021Review
- Computer-Aided Ligand Discovery for Estrogen Receptor Alpha.International journal of molecular sciences · 2020Review
- Emerging Roles and Therapeutic Interventions of Aerobic Glycolysis in Glioma.OncoTargets and therapy · 2020Review
- The Biological Role of the Collagen Alpha-3 (VI) Chain and Its Cleaved C5 Domain Fragment Endotrophin in Cancer.OncoTargets and therapy · 2020Review
- ERα, A Key Target for Cancer Therapy: A Review.OncoTargets and therapy · 2020Review
- Triple-high expression of phosphatase and tensin homolog (PTEN), estrogen receptor (ER) and progesterone receptor (PR) may predict favorable prognosis for patients with Type I endometrial carcinoma.Journal of Cancer · 2020Article
- Article
- Therapeutic applications of CRISPR/Cas9 in breast cancer and delivery potential of gold nanomaterials.NanobiomedicineArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Naturally-occurring somatic mutations in the estrogen receptor gene (ESR1) have been previously implicated in the clinical development of resistance to hormonal therapies, such as Tamoxifen. For example, the somatic mutation Y537S has been specifically associated with acquired endocrine resistance. Briefly, we recombinantly-transduced MCF7 cells with a lentiviral vector encoding ESR1 (Y537S). As a first step, we confirmed that MCF7-Y537S cells are indeed functionally resistant to Tamoxifen, as compared with vector alone controls. Importantly, further phenotypic characterization of Y537S cells revealed that they show increased resistance to Tamoxifen-induced apoptosis, allowing them to form mammospheres with higher efficiency, in the presence of Tamoxifen. Similarly, Y537S cells had elevated basal levels of ALDH activity, a marker of "stemness", which was also Tamoxifen-resistant. Metabolic flux analysis of Y537S cells revealed a hyper-metabolic phenotype, with significantly increased mitochondrial respiration and high ATP production, as well as enhanced aerobic glycolysis. Finally, to understand which molecular signaling pathways that may be hyper-activated in Y537S cells, we performed unbiased label-free proteomics analysis. Our results indicate that TIGAR over-expression and the Rho-GDI/PTEN signaling pathway appear to be selectively activated by the Y537S mutation. Remarkably, this profile is nearly identical in MCF7-TAMR cells; these cells were independently-generated
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.