ArticleCancer discovery2020
Global Regulation of the Histone Mark H3K36me2 Underlies Epithelial Plasticity and Metastatic Progression.
Article in Cancer discovery, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
59 citing papers in PubMed, 90 citations in OpenAlex.
- Decoding epithelial-mesenchymal transitions with multi-omics.Nature reviews. Genetics · 2026Review
- Hypoxia-induced metastatic heterogeneity in pancreatic cancer.Nature communications · 2026Article
- Multiple distinct metastatic cell states are induced by epithelial-mesenchymal plasticity.bioRxiv : the preprint server for biology · 2026Article
- A human induced pluripotent stem cell model for the holistic study of epithelial-to-mesenchymal transitions.Nature methods · 2026Article
- NSD2 upregulation is driven by high-risk HPV E6/E7 and disrupts epithelial differentiation in HPV-associated head and neck cancer.Journal of experimental & clinical cancer research : CR · 2026Article
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- Programming of the respiratory epitheliummedRxiv : the preprint server for health sciences · 2025Article
- Hypoxia-induced metastatic heterogeneity in pancreatic cancer.Research square · 2025Article
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- H3K36me2 methyltransferase NSD2/WHSC1 promotes triple-negative breast cancer metastasis via activation of ULK1-dependent autophagy.Autophagy · 2025Article
- Metastatic heterogeneity in pancreatic cancer: mechanisms and opportunities for targeted intervention.The Journal of clinical investigation · 2025Review
- In vivo CRISPR screening reveals epigenetic regulators of hepatobiliary plasticity.Genes & development · 2025Article
- NSD2 and miRNAs as Key Regulators of Melanoma Response to Romidepsin and Interferon-α2b Treatment.Cancer medicine · 2025Article
- Genetics and biology of pancreatic ductal adenocarcinoma.Genes & development · 2025Review
- Recruitment of FBXO22 for targeted degradation of NSD2.Nature chemical biology · 2024Article
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- Rewriting cellular fate: epigenetic interventions in obesity and cellular programming.Molecular medicine (Cambridge, Mass.) · 2024Review
- ISWI chromatin remodeling complexes recruit NSD2 and H3K36me2 in pericentromeric heterochromatin.The Journal of cell biology · 2024Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 1 country.
Funding
Abstract
Epithelial plasticity, reversible modulation of a cell's epithelial and mesenchymal features, is associated with tumor metastasis and chemoresistance, leading causes of cancer mortality. Although different master transcription factors and epigenetic modifiers have been implicated in this process in various contexts, the extent to which a unifying, generalized mechanism of transcriptional regulation underlies epithelial plasticity remains largely unknown. Here, through targeted CRISPR/Cas9 screening, we discovered two histone-modifying enzymes involved in the writing and erasing of H3K36me2 that act reciprocally to regulate epithelial-to-mesenchymal identity, tumor differentiation, and metastasis. Using a lysine-to-methionine histone mutant to directly inhibit H3K36me2, we found that global modulation of the mark is a conserved mechanism underlying the mesenchymal state in various contexts. Mechanistically, regulation of H3K36me2 reprograms enhancers associated with master regulators of epithelial-to-mesenchymal state. Our results thus outline a unifying epigenome-scale mechanism by which a specific histone modification regulates cellular plasticity and metastasis in cancer. SIGNIFICANCE: Although epithelial plasticity contributes to cancer metastasis and chemoresistance, no strategies exist for pharmacologically inhibiting the process. Here, we show that global regulation of a specific histone mark, H3K36me2, is a universal epigenome-wide mechanism that underlies epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition in carcinoma cells. These results offer a new strategy for targeting epithelial plasticity in cancer.
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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.