ArticleBMC cancer2014
Benzyl butyl phthalate induces migration, invasion, and angiogenesis of Huh7 hepatocellular carcinoma cells through nongenomic AhR/G-protein signaling.
Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 43 citations in OpenAlex.
- Endocrine disruption to metastasis: How phthalates promote breast carcinogenesis.Ecotoxicology and environmental safety · 2025Review
- The AhR pathway regulation in phthalates-induced cancer promotion, progression and metastasis: a scoping review.Cancer cell international · 2025Review
- Lung cancer associated with combustion particles and fine particulate matter (PMBiochemical pharmacology · 2023Review
- Kynurenine promotes neonatal heart regeneration by stimulating cardiomyocyte proliferation and cardiac angiogenesis.Nature communications · 2022Article
- Prenatal exposure to the phthalate DEHP impacts reproduction-related gene expression in the pituitary.Reproductive toxicology (Elmsford, N.Y.) · 2022Article
- Endoglin Modulates TGFβR2 Induced VEGF and Proinflammatory Cytokine Axis Mediated Angiogenesis in Prolonged DEHP-Exposed Breast Cancer Cells.Biomedicines · 2022Article
- Endogenous regulation of the Akt pathway by the aryl hydrocarbon receptor (AhR) in lung fibroblasts.Scientific reports · 2021Article
- 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
- Structure-Dependent Effects of Phthalates on Intercellular and Intracellular Communication in Liver Oval Cells.International journal of molecular sciences · 2020Article
- A moderate physiological dose of benzyl butyl phthalate exacerbates the high fat diet-induced diabesity in male mice.Toxicology research · 2020Article
- Kynurenic acid and cancer: facts and controversies.Cellular and molecular life sciences : CMLS · 2020Review
- Role of Resveratrol on Indoxyl Sulfate-Induced Endothelial Hyperpermeability via Aryl Hydrocarbon Receptor (AHR)/Src-Dependent Pathway.Oxidative medicine and cellular longevity · 2019Article
- Investigation of the aryl hydrocarbon receptor and the intrinsic tumoral component of the kynurenine pathway of tryptophan metabolism in primary brain tumors.Journal of neuro-oncology · 2018Article
- Aryl Hydrocarbon Receptor Promotes IL-10 Expression in Inflammatory Macrophages Through Src-STAT3 Signaling Pathway.Frontiers in immunology · 2018Article
- Cytoplasmic aryl hydrocarbon receptor regulates glycogen synthase kinase 3 beta, accelerates vimentin degradation, and suppresses epithelial-mesenchymal transition in non-small cell lung cancer cells.Archives of toxicology · 2017Article
- Multimodal imaging of a humanized orthotopic model of hepatocellular carcinoma in immunodeficient mice.Scientific reports · 2016Article
- MALDI imaging reveals NCOA7 as a potential biomarker in oral squamous cell carcinoma arising from oral submucous fibrosis.Oncotarget · 2016Article
- Benzyl butyl phthalate promotes breast cancer stem cell expansion via SPHK1/S1P/S1PR3 signaling.Oncotarget · 2016Article
- Knockdown of Golgi phosphoprotein 2 inhibits hepatocellular carcinoma cell proliferation and motility.Oncotarget · 2016Article
- NF-κB signaling pathway confers neuroblastoma cells migration and invasion ability via the regulation of CXCR4.Medical science monitor : international medical journal of experimental and clinical research · 2014Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe widespread use of phthalates as plasticizers has raised public health concerns regarding their adverse effects, including an association with cancer. Although animal investigations have suggested an association between phthalate exposure and hepatocellular carcinoma, the mechanisms are unknown.
methodsThe hepatocellular carcinoma cell line Huh7 was treated with benzyl butyl phthalate (BBP), and then analyzed by total internal reflection fluorescence microscopy, confocal microscopy and double immunogold transmission electron microscopy. Following BBP treatment, mRNA levels were measured by RT-PCR, protein levels were measured using western blot, and vascular endothelial growth factor levels were measured by an enzyme-linked immunosorbent assay. Cell migration and invasion assays were evaluated by transwell, and angiogenesis were performed by a tube formation assay. Nude mice were used to investigate metastasis and angiogenesis in vivo.
resultsBBP affected hepatocellular carcinoma progression through the aryl hydrocarbon receptor (AhR) and that benzyl butyl phthalate (BBP) stimulated AhR at the cell surface, which then interacted with G proteins and triggered a downstream signaling cascade. BBP activated AhR through a nongenomic action involving G-protein signaling rather than the classical genomic AhR action. BBP treatment promoted cell migration and invasion in vitro and metastasis in vivo via the AhR/Gβ/PI3K/Akt/NF-κB pathway. In addition, BBP induced both in vitro and in vivo angiogenesis through the AhR/ERK/VEGF pathway.
conclusionsThese findings suggest a novel nongenomic AhR mechanism involving G-protein signaling induced by phthalates, which contributes to tumor progression of hepatocellular carcinoma.
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