ArticleGenome biology2015
Methylation-dependent SOX9 expression mediates invasion in human melanoma cells and is a negative prognostic factor in advanced melanoma.
Article in Genome biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 96 citations in OpenAlex.
- Epigenetic alterations in cancer metastasis: molecular mechanisms and implications for precision oncology.Frontiers in oncology · 2026Review
- Melanoma stem cells drive macrophage reprogramming to a hybrid phenotype, modulating melanoma stemness and compromising NK cell-mediated immunity.Frontiers in immunology · 2026Article
- Article
- Elevated NR2F1 underlies the persistence of invasive disease after treatment of BRAF-mutant melanoma.The Journal of clinical investigation · 2025Article
- Article
- SOX9: an important factor in regulating breast cancer.European journal of medical research · 2025Review
- SOX9 suppresses colon cancer via inhibiting epithelial-mesenchymal transition and SOX2 induction.The Journal of clinical investigation · 2025Article
- DNA Methylation Classes of Stage II and III Primary Melanomas and Their Clinical and Prognostic Significance.JCO precision oncology · 2024Article
- Glycolysis-related five-gene signature correlates with prognosis and immune infiltration in gastric cancer.World journal of gastrointestinal oncology · 2024Article
- Diverse functions of SOX9 in liver development and homeostasis and hepatobiliary diseases.Genes & diseases · 2024Review
- Harmony in chaos: understanding cancer through the lenses of developmental biology.Molecular oncology · 2024Article
- Identification of a CpG-based signature coupled with gene expression as prognostic indicators for melanoma: a preliminary study.Scientific reports · 2024Article
- Cell state dependent effects of Bmal1 on melanoma immunity and tumorigenicity.Nature communications · 2024Article
- Strategic Approach to Heterogeneity Analysis of Cutaneous Adnexal Carcinomas Using Computational Pathology and Genomics.JID innovations : skin science from molecules to population health · 2023Article
- Dynamical modeling of proliferative-invasive plasticity and IFNγ signaling in melanoma reveals mechanisms of PD-L1 expression heterogeneity.Journal for immunotherapy of cancer · 2023Article
- Dynamical modelling of proliferative-invasive plasticity and IFNγ signaling in melanoma reveals mechanisms of PD-L1 expression heterogeneity.bioRxiv : the preprint server for biology · 2023Article
- Tumour Suppressor Neuron Navigator 3 and Matrix Metalloproteinase 14 are Co-expressed in Most Melanomas but Downregulated in Thick Tumours.Acta dermato-venereologica · 2023Article
- Dishevelled Segment Polarity Protein 3: A Novel Prognosis-related Marker in Pan-driver-gene-negative Lung Adenocarcinoma.Journal of Cancer · 2023Article
- RNA-seq and ChIP-seq Identification of Unique and Overlapping Targets of GLI Transcription Factors in Melanoma Cell Lines.Cancers · 2022Article
- SOX9 in organogenesis: shared and unique transcriptional functions.Cellular and molecular life sciences : CMLS · 2022Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMelanoma is the most fatal skin cancer displaying a high degree of molecular heterogeneity. Phenotype switching is a mechanism that contributes to melanoma heterogeneity by altering transcription profiles for the transition between states of proliferation/differentiation and invasion/stemness. As phenotype switching is reversible, epigenetic mechanisms, like DNA methylation, could contribute to the changes in gene expression.
resultsIntegrative analysis of methylation and gene expression datasets of five proliferative and five invasion melanoma cell cultures reveal two distinct clusters. SOX9 is methylated and lowly expressed in the highly proliferative group. SOX9 overexpression results in decreased proliferation but increased invasion in vitro. In a B16 mouse model, sox9 overexpression increases the number of lung metastases. Transcriptional analysis of SOX9-overexpressing melanoma cells reveals enrichment in epithelial to mesenchymal transition (EMT) pathways. Survival analysis of The Cancer Genome Atlas melanoma dataset shows that metastatic patients with high expression levels of SOX9 have significantly worse survival rates. Additional survival analysis on the targets of SOX9 reveals that most SOX9 downregulated genes have survival benefit for metastatic patients.
conclusionsOur genome-wide DNA methylation and gene expression study of 10 early passage melanoma cell cultures reveals two phenotypically distinct groups. One of the genes regulated by DNA methylation between the two groups is SOX9. SOX9 induces melanoma cell invasion and metastasis and decreases patient survival. A number of genes downregulated by SOX9 have a negative impact on patient survival. In conclusion, SOX9 is an important gene involved in melanoma invasion and negatively impacts melanoma patient survival.
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