ArticleOncotarget2016
Inverse agonist of estrogen-related receptor α suppresses the growth of triple negative breast cancer cells through ROS generation and interaction with multiple cell signaling pathways.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 35 citations in OpenAlex.
- Oxidative Stress in Breast Cancer: A Biochemical Map of Reactive Oxygen Species Production.Current issues in molecular biology · 2024Review
- Estrogen-Related Receptor Alpha (ERRα) Promotes Cancer Stem Cell-Like Characteristics in Breast Cancer.Stem cell reviews and reports · 2023Article
- Targeting Estrogen Signaling in the Radiation-induced Neurodegeneration: A Possible Role of Phytoestrogens.Current neuropharmacology · 2023Review
- Estrogen-related receptor alpha in select host functions and cancer: new frontiers.Molecular and cellular biochemistry · 2022Review
- Targeting Apoptosis in Cancer.Current oncology reports · 2022Review
- Estrogen-related Receptor α (ERRα) Functions in The Hypoxic Injury of Microglial Cells.Journal of veterinary research · 2022Article
- Treatment Strategies Against Triple-Negative Breast Cancer: An Updated Review.Breast cancer (Dove Medical Press) · 2022Review
- Review
- Targeting the Mitochondrial Metabolic Network: A Promising Strategy in Cancer Treatment.International journal of molecular sciences · 2020Review
- Exploring the binding mode and thermodynamics of inverse agonists against estrogen-related receptor alpha.RSC advances · 2020Article
- Estrogen-related receptors are targetable ROS sensors.Genes & development · 2020Article
- Involvement of CHOP in activin A‑induced myeloma NS‑1 cell apoptosis.Oncology reports · 2019Article
- Regulatory mechanisms leading to differential Acyl-CoA synthetase 4 expression in breast cancer cells.Scientific reports · 2019Article
- Antitumor effect of XCT790, an ERRα inverse agonist, on ERα-negative endometrial cancer cells.Cellular oncology (Dordrecht, Netherlands) · 2019Article
- Identification of Compounds That Inhibit Estrogen-Related Receptor Alpha Signaling Using High-Throughput Screening Assays.Molecules (Basel, Switzerland) · 2019Article
- MAT2B expression correlates with poor prognosis in triple-negative breast cancer.Cancer management and research · 2019Article
- Novel endocrine therapeutic strategy in endometrial carcinoma targeting estrogen-related receptor α by XCT790 and siRNA.Cancer management and research · 2018Article
- The down-regulation of SLC7A11 enhances ROS induced P-gp over-expression and drug resistance in MCF-7 breast cancer cells.Scientific reports · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is an urgent clinical need for targeted therapy approaches for triple-negative breast cancer (TNBC) patients. Increasing evidences suggested that the expression of estrogen-related receptor alpha (ERRα) was correlate with unfavorable clinical outcomes of breast cancer patients. We here show that inhibition of ERRα by its inverse agonist XCT-790 can suppress the proliferation, decrease G2/M phases, and induce mitochondrial-related apoptosis of TNBC cells. XCT-790 elevates the proteins related to endoplasmic reticulum (ER) stress such as ATF4/6, XBT-1 and CHOP. It also increases the expression of growth inhibition related proteins such as p53 and p21. Further, XCT-790 can increase the generation of reactive oxygen species (ROS) in TNBC cells mainly through inhibition of SOD1/2. While ROS scavenger NAC abolishes XCT-790 induced ER-stress and growth arrest. XCT-790 treatment can rapidly activate the signal molecules including ERK1/2, p38-MAPK, JNK, Akt, p65, and IκBα, while NAC attenuates effects of XCT-790 induced phosphorylation of ERK1/2, p38-MAPK and Akt. Further, the inhibitors of ERK1/2, JNK, Akt, and NF-κB attenuate XCT-790 induced ROS generation. These data suggest that AKT/ROS and ERK/ROS positive feedback loops, NF-κB/ROS, and ROS/p38-MAPK, are activated in XCT-790 treated TNBC cells. In vivo experiments show that XCT-790 significantly suppresses the growth of MDA-MB-231 xenograft tumors, which is associated with up regulation of p53, p21, ER-stress related proteins while down regulation of bcl-2. The present discovery makes XCT-790 a promising candidate drug and lays the foundation for future development of ERRα-based therapies for TNBC patients.
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.