ArticleLaboratory investigation; a journal of technical methods and pathology2021
Bone morphogenetic protein induces bone invasion of melanoma by epithelial-mesenchymal transition via the Smad1/5 signaling pathway.
Article in Laboratory investigation; a journal of technical methods and pathology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 44 citations in OpenAlex.
- In vitro multi-organ invasion model for exploring cardiac resistance to cancer metastasis.Nature communications · 2026Article
- Bone morphogenetic proteins (BMPs) at the forefront of ocular diseases and therapeutics.Eye and vision (London, England) · 2025Review
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- RUNX1-BMP2 promotes vasculogenic mimicry in laryngeal squamous cell carcinoma via activation of the PI3K-AKT signaling pathway.Cell communication and signaling : CCS · 2024Article
- The Interaction Between SMAD1 and YAP1 Is Correlated with Increased Resistance of Gastric Cancer Cells to Cisplatin.Applied biochemistry and biotechnology · 2023Article
- An Early Neoplasia Index (ENI10), Based on Molecular Identity of CD10 Cells and Associated Stemness Biomarkers, is a Predictor of Patient Outcome in Many Cancers.Cancer research communications · 2023Article
- Functions of the bone morphogenetic protein signaling pathway through non-coding RNAs.Non-coding RNA research · 2022Review
- Construction and Validation of a Ferroptosis-Related Prognostic Signature for Melanoma Based on Single-Cell RNA Sequencing.Frontiers in cell and developmental biology · 2022Article
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Authors and funding
19 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Oral malignant melanoma, which frequently invades the hard palate or maxillary bone, is extremely rare and has a poor prognosis. Bone morphogenetic protein (BMP) is abundantly expressed in bone matrix and is highly expressed in malignant melanoma, inducing an aggressive phenotype. We examined the role of BMP signaling in the acquisition of an aggressive phenotype in melanoma cells in vitro and in vivo. In five cases, immunohistochemistry indicated the phosphorylation of Smad1/5 (p-Smad1/5) in the nuclei of melanoma cells. In the B16 mouse and A2058 human melanoma cell lines, BMP2, BMP4, or BMP7 induces morphological changes accompanied by the downregulation of E-cadherin, and the upregulation of N-cadherin and Snail, markers of epithelial-mesenchymal transition (EMT). BMP2 also stimulates cell invasion by increasing matrix metalloproteinase activity in B16 cells. These effects were canceled by the addition of LDN193189, a specific inhibitor of Smad1/5 signaling. In vivo, the injection of B16 cells expressing constitutively activated ALK3 enhanced zygoma destruction in comparison to empty B16 cells by increasing osteoclast numbers. These results suggest that the activation of BMP signaling induces EMT, thus driving the acquisition of an aggressive phenotype in malignant melanoma.
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