ArticleOncotarget2016
Benzyl butyl phthalate promotes breast cancer stem cell expansion via SPHK1/S1P/S1PR3 signaling.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- A systematic review on the adverse health effects of di-2-ethylhexyl phthalate.Environmental science and pollution research international · 2016Pooled it
- Integrative network toxicology and experimental evidence reveal mechanisms underlying diethyl phthalate-induced initiation and progression of endometrial cancer.Scientific reports · 2026Article
- Targeting Sphingolipids in Breast Cancer: From Tumor Biology to Therapeutic Strategies.Oncology research · 2026Review
- Whole-exome sequencing for identification of specific gene mutations in an Indian cohort of triple-negative breast cancer patients.Discover oncology · 2025Article
- Sphingosine 1-phosphate signalling in cancer stem cells.Oncogenesis · 2025Review
- Computer-Aided Molecular Design Meets Network Toxicology and Molecular Docking: A Joint Strategy to Explore Common Molecular Mechanisms of Phthalates on Human Breast Cancer and Structure-Activity Relationship.International journal of molecular sciences · 2025Article
- Dysregulation of microRNA (miRNA) Due to Phthalate/Phthalate Metabolite Exposure and Associated Health Effects: A Narrative Review.Journal of xenobiotics · 2025Review
- The AhR pathway regulation in phthalates-induced cancer promotion, progression and metastasis: a scoping review.Cancer cell international · 2025Review
- Targeting SNAI1-Mediated Colorectal Cancer Chemoresistance and Stemness by Sphingosine Kinase 2 Inhibition.World journal of oncology · 2024Article
- The Dual Faces of Oestrogen: The Impact of Exogenous Oestrogen on the Physiological and Pathophysiological Functions of Tissues and Organs.International journal of molecular sciences · 2024Review
- Next-generation of BBQ analogues that selectively target breast cancer.Frontiers in chemistry · 2024Article
- Association of Serum Levels of Plasticizers Compounds, Phthalates and Bisphenols, in Patients and Survivors of Breast Cancer: A Real Connection?International journal of environmental research and public health · 2022Article
- Sphingolipid metabolism in the development and progression of cancer: one cancer's help is another's hindrance.Molecular oncology · 2021Review
- Heterogeneity of BCSCs contributes to the metastatic organotropism of breast cancer.Journal of experimental & clinical cancer research : CR · 2021Review
- Mechanistic insight into toxicity of phthalates, the involved receptors, and the role of Nrf2, NF-κB, and PI3K/AKT signaling pathways.Environmental science and pollution research international · 2021Review
- Divergence of Intracellular Trafficking of Sphingosine Kinase 1 and Sphingosine-1-Phosphate Receptor 3 in MCF-7 Breast Cancer Cells and MCF-7-Derived Stem Cell-Enriched Mammospheres.International journal of molecular sciences · 2021Article
- Epimutational effects of electronic cigarettes.Environmental science and pollution research international · 2021Review
- The Importance of Sphingosine Kinase in Breast Cancer: A Potential for Breast Cancer Management.Cureus · 2021Review
- Sphingosine Kinase 1 Signaling in Breast Cancer: A Potential Target to Tackle Breast Cancer Stem Cells.Frontiers in molecular biosciences · 2021Review
- Environmental chemicals, breast cancer progression and drug resistance.Environmental health : a global access science source · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding the regulatory mechanisms unique to breast cancer stem cells (BCSCs) is required to control breast cancer metastasis. We found that phthalates promote BCSCs in human breast cancer cell cultures and xenograft tumors. A toxic phthalate, benzyl butyl phthalate (BBP), activated aryl hydrocarbon receptor in breast cancer cells to stimulate sphingosine kinase 1 (SPHK1)/sphingosine 1-phosphate (S1P)/sphingosine-1-phosphate receptor 3 (S1PR3) signaling and enhance formation of metastasis-initiating BCSCs. BBP induced histone modifications in S1PR3 in side population (SP) cells, but not in non-SP cells. SPHK1 or S1PR3 knockdown in breast cancer cells effectively reduced tumor growth and lung metastasis in vivo. Our findings suggest S1PR3 is a determinant of phthalate-driven breast cancer metastasis and a possible therapeutic target for regulating BCSC populations. Furthermore, the association between breast carcinogenesis and environmental pollutants has important implications for public health.
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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.