Omics · study · 2026
Oncogenic Ras signaling disrupts PRC2 via EED downregulation to drive oncogenic reprogramming and niche remodeling in squamous cell carcinoma
Listed in NCBI GEO
Squamous cell carcinoma (SCC) is a common epithelial malignancy, yet its epigenetic underpinnings remain poorly defined.
Description
Here, we identify the Polycomb Repressive Complex 2 (PRC2) as a key epigenetic barrier of SCC tumorigenesis. Despite high EZH2 levels, the PRC2-dependent H3K27me3 is depleted in human and murine SCCs, indicating complex destabilization rather than enzymatic failure.
Mechanistically, oncogenic Ras signaling downregulates the PRC2 scaffolding subunit EED, disrupting PRC2 and H3K27me3 and activating oncogenic loci. Depletion of Eed in epidermal progenitors disrupts the proliferation–differentiation balance and, upon carcinogen exposure, drives invasive SCC. Single-cell RNA-seq of Eed-deficient tumors reveals an expansion of tumor-specific keratinocytes and a remodeled pro-tumorigenic microenvironment.
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Notably, reintroducing EED in SCC cells restores PRC2 integrity and H3K27me3 levels, suppressing tumor growth and mitigating the pro-tumorigenic niche. Our findings establish PRC2 as an essential epigenetic gatekeeper in SCC and suggest restoring PRC2-mediated repression may offer a novel therapeutic strategy.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE304nnn/GSE304812 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE304812 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1302787 ncbi.nlm.nih.gov/bioproject/PRJNA1302787 ↗
project · from NCBI GEO
- PubMed 42443217 pubmed.ncbi.nlm.nih.gov/42443217 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Cancer 65% · RNA sequencing 65% · Single-cell RNA sequencing 65%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE304812 | 15 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[modality].local:modality:single-cell-rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |