Omics · study · 2026
ZNF274 constrains lineage plasticity and drives intrinsic resistance to CDK7 inhibitors in pancreatic cancer
Listed in NCBI GEO
Pancreatic Ductal Adenocarcinoma (PDAC) is characterized by two distinct transcriptional subtypes: classical and basal, which may interconvert.
Description
We show the KRAB-ZNF protein, ZNF274, correlates with PDAC subtype and regulates sensitivity to CDK7 inhibition by facilitating heterochromatin maintenance and gene suppression. We find ZNF274 loss drives a classical to basal transition, induces invasive protrusions and facilitates invasion capacity.
We define two mechanistic arms to this regulation. ZNF274 directly suppresses ZEB1 expression. When ZNF274 is lost, ZEB1 facilitates acquisition of mesenchymal features, keratin gene expression, and susceptibility to CDK7 inhibition.
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Second, ZNF274 dampens expression of repetitive elements including human endogenous retroviruses (HERVs). HERV expression following ZNF274 loss induces a double stranded RNA response that reinforces the classical to basal subtype transition. Here, we show ZNF274 is an important epigenetic regulator of cellular plasticity and sensitivity to CDK7 inhibition, presenting a therapeutic liability of PDAC subtype transition that is actionable in the clinic.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE285nnn/GSE285406 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE285406 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1203584 ncbi.nlm.nih.gov/bioproject/PRJNA1203584 ↗
project · from NCBI GEO
- PubMed 42177198 pubmed.ncbi.nlm.nih.gov/42177198 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Genome binding/occupancy profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE285406 | 11 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:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| 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:9606 | 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 |