ArticleScientific reports2016
Smad6 determines BMP-regulated invasive behaviour of breast cancer cells in a zebrafish xenograft model.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 46 citations in OpenAlex.
- Preclinical models of breast cancer metastasis: strengths, limitations, and clinical relevance.NPJ breast cancer · 2026Review
- Robust statistical assessment of Oncogenotype to Organotropism translation in xenografted zebrafish.bioRxiv : the preprint server for biology · 2025Article
- LncRNA PVT1 activated by TGF-β1/Smad3 facilitates proliferation and metastasis of hepatocellular carcinoma via upregulating Smad6 and NRG1.Journal of translational medicine · 2025Article
- Development of a Triple-Negative Breast Cancer Leptomeningeal Disease Model in Zebrafish.Cells · 2023Article
- PCB: A pseudotemporal causality-based Bayesian approach to identify EMT-associated regulatory relationships of AS events and RBPs during breast cancer progression.PLoS computational biology · 2023Article
- A MYC-ZNF148-ID1/3 regulatory axis modulating cancer stem cell traits in aggressive breast cancer.Oncogenesis · 2022Article
- Comprehensive genomics in androgen receptor-dependent castration-resistant prostate cancer identifies an adaptation pathway mediated by opioid receptor kappa 1.Communications biology · 2022Article
- Natural killer cell-derived exosomal miR-1249-3p attenuates insulin resistance and inflammation in mouse models of type 2 diabetes.Signal transduction and targeted therapy · 2021Article
- Zebrafish models of acute leukemias: Current models and future directions.Wiley interdisciplinary reviews. Developmental biology · 2021Review
- Prognostic impact of the glypican family of heparan sulfate proteoglycans on the survival of breast cancer patients.Journal of cancer research and clinical oncology · 2021Article
- How to Make a Rodent Giant: Genomic Basis and Tradeoffs of Gigantism in the Capybara, the World's Largest Rodent.Molecular biology and evolution · 2021Article
- Circular RNA hsa_circ_0000517 modulates hepatocellular carcinoma advancement via the miR-326/SMAD6 axis.Cancer cell international · 2020Article
- SMAD6, positively regulated by the DNM3OS-miR-134-5p axis, confers promoting effects to cell proliferation, migration and EMT process in retinoblastoma.Cancer cell international · 2020Article
- Zebrafish Models of Cancer-New Insights on Modeling Human Cancer in a Non-Mammalian Vertebrate.Genes · 2019Review
- GREM1 is associated with metastasis and predicts poor prognosis in ER-negative breast cancer patients.Cell communication and signaling : CCS · 2019Article
- Integrated transcriptomics reveals master regulators of lung adenocarcinoma and novel repositioning of drug candidates.Cancer medicine · 2019Article
- Inflammation induces endothelial-to-mesenchymal transition and promotes vascular calcification through downregulation of BMPR2.The Journal of pathology · 2019Article
- Nuclear Smad6 promotes gliomagenesis by negatively regulating PIAS3-mediated STAT3 inhibition.Nature communications · 2018Article
- Embryonic zebrafish xenograft assay of human cancer metastasis.F1000Research · 2018Article
- TGF-β Family Signaling in Tumor Suppression and Cancer Progression.Cold Spring Harbor perspectives in biology · 2017Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transforming growth factor-β (TGF-β) family is known to play critical roles in cancer progression. While the dual role of TGF-β is well described, the function of bone morphogenetic proteins (BMPs) is unclear. In this study, we established the involvement of Smad6, a BMP-specific inhibitory Smad, in breast cancer cell invasion. We show that stable overexpression of Smad6 in breast cancer MCF10A M2 cells inhibits BMP signalling, thereby mitigating BMP6-induced suppression of mesenchymal marker expression. Using a zebrafish xenograft model, we demonstrate that overexpression of Smad6 potentiates invasion of MCF10A M2 cells and enhances the aggressiveness of breast cancer MDA-MB-231 cells in vivo, whereas a reversed phenotype is observed after Smad6 knockdown. Interestingly, BMP6 pre-treatment of MDA-MB-231 cells induced cluster formation at the invasive site in the zebrafish. BMP6 also stimulated cluster formation of MDA-MB-231 cells co-cultured on Human Microvascular Endothelial Cells (HMEC)-1 in vitro. Electron microscopy illustrated an induction of cell-cell contact by BMP6. The clinical relevance of our findings is highlighted by a correlation of high Smad6 expression with poor distant metastasis free survival in ER-negative cancer patients. Collectively, our data strongly indicates the involvement of Smad6 and BMP signalling in breast cancer cell invasion in vivo.
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