Omics · study · 2026
EZH2 cooperates with SREBP2 to establish the epigenomic, transcriptomic and metabolic programs for driving oncogenesis [CUT&Tag I]
Listed in NCBI GEO
Enhancer of Zeste Homolog 2 (EZH2) is recurrently overexpressed in cancers, correlating with adverse clinical outcomes.
Description
How exactly EZH2 overexpression contributes to tumorigenicity is far from clear. We here report an unexplored tumor-promoting axis involving the EZH2 association with SREBP2, a master regulator of lipid metabolism.
EZH2 and SREBP2 act together to potentiate the expression of mevalonate pathway genes, thereby enhancing cholesterol biosynthesis to sustain aggressive tumor growth. The partially disordered transcriptional activation domains (tADs) of EZH2 and SREBP2 directly bind and recruit p300 to mediate the proto-oncogene activation. Additionally, we employed Proteolysis Targeting Chimeras (PROTACs) to block such a noncanonical function of EZH2 in cancer.
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Independent EZH2-targeting PROTACs degraded EZH2 and SREBP2 both and downregulated the SREBP2-associated gene-expression program, leading to inhibition of tumor growth. Altogether, this study unveils the existence of an EZH2:SREBP2 axis in cancers, which operates to sustain tumorigenesis via promoting cholesterol metabolism, paradigm-shifting the current understanding of EZH2’s oncogenic functions.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE287nnn/GSE287353 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE287353 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1212205 ncbi.nlm.nih.gov/bioproject/PRJNA1212205 ↗
project · from NCBI GEO
- PubMed 42601451 pubmed.ncbi.nlm.nih.gov/42601451 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Genome binding/occupancy profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE287353 | 13 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 (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:genome-binding-occupancy-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| 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 |