ArticleThe Journal of clinical investigation2020
H3K27me3-mediated PGC1α gene silencing promotes melanoma invasion through WNT5A and YAP.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 58 citations in OpenAlex.
- Epigenetically silencing gluconeogenic enzyme PCK1 by EZH2 promotes renal tubulointerstitial fibrosis.Molecular biomedicine · 2026Article
- Boric Acid Induces Oxidative Stress-Associated Cytotoxicity and Modulates Wnt Signaling in MALME-3M Cells.Biological trace element research · 2026Article
- MAPK Inhibitor-Tolerant Persister Cells in Melanoma: Mechanisms and Therapeutic Vulnerabilities.Cancer science · 2026Review
- Molecular reprogramming in cutaneous melanoma: the central role of G9a and EZH2 methyltransferase inhibitors in tumor plasticity, immune evasion, and therapeutic resistance.Frontiers in pharmacology · 2026Review
- EZH2 in Acral Lentiginous Melanoma: Molecular, Epigenetic, and Therapeutic Perspectives.Oncology research · 2026Review
- A methyl-to-acetyl switch in H3K27 drives metabolic reprogramming and resistance to BRAFNeoplasia (New York, N.Y.) · 2025Article
- Mitochondrial bioenergetics and networks in melanoma: an update.Apoptosis : an international journal on programmed cell death · 2025Review
- Primary pulmonary malignant melanoma with H3K27Me3 loss: A case report.Oncology letters · 2025Article
- Unleashing Wnts: Wnt Ligands Fuel Cancer Spread.Journal of cancer biology · 2025Article
- PGC-1α drives small cell neuroendocrine cancer progression toward an ASCL1-expressing subtype with increased mitochondrial capacity.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- TCF12-regulated GRB7 facilitates the HER2+ breast cancer progression by activating Notch1 signaling pathway.Journal of translational medicine · 2024Article
- MiR26a reverses enzalutamide resistance in a bone-tumor targeted system with an enhanced effect on bone metastatic CRPC.Journal of nanobiotechnology · 2024Article
- Independent organelle and organelle-organelle interactions: essential mechanisms for malignant gynecological cancer cell survival.Frontiers in immunology · 2024Review
- From metabolism to malignancy: the multifaceted role of PGC1α in cancer.Frontiers in oncology · 2024Review
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- Altered expression, but small contribution, of the histone demethylase KDM6A in obstructive uropathy in mice.Disease models & mechanisms · 2023Article
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- Epigenetic suppression of PGC1α (PPARGC1A) causes collateral sensitivity to HMGCR-inhibitors within BRAF-treatment resistant melanomas.Nature communications · 2023Article
- WNT5a Signaling through ROR2 Activates the Hippo Pathway to Suppress YAP1 Activity and Tumor Growth.Cancer research · 2023Article
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Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Oncogene-targeted and immune checkpoint therapies have revolutionized the clinical management of malignant melanoma and now offer hope to patients with advanced disease. Intimately connected to patients' overall clinical risk is whether the initial primary melanoma lesion will metastasize and cause advanced disease, but underlying mechanisms are not entirely understood. A subset of melanomas display heightened peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1α) expression that maintains cell survival cues by promoting mitochondrial function, but also suppresses metastatic spread. Here, we show that PGC1α expression in melanoma cells was silenced by chromatin modifications that involve promoter H3K27 trimethylation. Pharmacological EZH2 inhibition diminished H3K27me3 histone markers, increased PGC1α expression, and functionally suppressed invasion within PGC1α-silenced melanoma cells. Mechanistically, PGC1α silencing activated transcription factor 12 (TCF12), to increase expression of WNT5A, which in turn stabilized YAP protein levels to promote melanoma migration and metastasis. Accordingly, inhibition of components of this transcription-signaling axis, including TCF12, WNT5A, or YAP, blocked melanoma migration in vitro and metastasis in vivo. These results indicate that epigenetic control of melanoma metastasis involved altered expression of PGC1α and an association with the inherent metabolic state of the tumor.
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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.