ArticleThe Journal of investigative dermatology2022
Merkel Cell Carcinoma Sensitivity to EZH2 Inhibition Is Mediated by SIX1 Derepression.
Article in The Journal of investigative dermatology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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The trial behind it
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Who cites it
10 citing papers in PubMed, 19 citations in OpenAlex.
- Diagnostic Utility and Clinicopathologic Associations of Histone H3 Lysine 27 Trimethylation (H3K27me3) Immunohistochemistry for Merkel Cell Carcinoma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2026Article
- Pharmacologic reversion of Merkel cell carcinoma via CBP/p300 inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Integrative analysis reveals therapeutic potential of pyrvinium pamoate in Merkel cell carcinoma.The Journal of clinical investigation · 2025Article
- Integrative analysis reveals therapeutic potential of pyrvinium pamoate in Merkel cell carcinoma.bioRxiv : the preprint server for biology · 2024Article
- Advancing Treatment Options for Merkel Cell Carcinoma: A Review of Tumor-Targeted Therapies.International journal of molecular sciences · 2024Review
- Lineage-specific canonical and non-canonical activity of EZH2 in advanced prostate cancer subtypes.Nature communications · 2024Article
- Merkel cell carcinoma: updates in tumor biology, emerging therapies, and preclinical models.Frontiers in oncology · 2024Review
- Polycomb Directed Cell Fate Decisions in Development and Cancer.Epigenomes · 2022Review
- Reversal of viral and epigenetic HLA class I repression in Merkel cell carcinoma.The Journal of clinical investigation · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Polycomb repressive complex 2 has a critical role in the maintenance of bivalent promoters and is often perturbed in cancer, including neuroendocrine tumors. In this study, we investigated the susceptibility of Merkel cell carcinoma (MCC), a neuroendocrine carcinoma of the skin, to inhibitors of the Polycomb repressive complex 2 catalytic subunit EZH2. We show that a subset of MCC cell lines is sensitive to EZH2 inhibitor-induced cell viability loss. We find that inhibitor treatment of susceptible cells derepresses the Polycomb repressive complex 2 target SIX1, a transcription factor in the PAX-SIX-EYA-DACH network normally involved in inner ear hair cell development, and that PAX-SIX-EYA-DACH network transcription factors are critical contributors to EZH2 inhibitor-induced MCC cell viability loss. Furthermore, we show the EZH2 inhibitor tazemetostat slows the growth of MCC xenografts and derepresses SIX1 and its downstream inner ear transcriptional target MYO6 in vivo. We propose that EZH2 inhibition in MCC leads to SIX1 derepression with dysregulation of hearing-related transcriptional programs and growth inhibition. This study provides evidence that MCC tumors may be specifically susceptible to EZH2 inhibitors, while giving mechanistic insight into the transcriptional programs these inhibitors perturb in MCC, and potentially in other neuroendocrine cancers.
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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 Socratic graph.