Omics · study · 2026
A Druggable TGF-β-Mediated Stromal Programming Axis in ATM-Deficient Pancreatic Cancer
Listed in NCBI GEO
The tumor microenvironment (TME) actively contributes to pancreatic ductal adenocarcinoma (PDAC) pathogenesis via a dynamic bidirectional tumor–stroma dialog.
Description
Here, we show that homologous recombination-defective (HRD) neoplastic epithelium reprograms its TME in a genotype-specific manner to promote cancer aggressiveness. Autochthonous mouse models, co-culture systems, single-nucleus multiomics investigations and human PDAC specimens revealed that tumoral ATM serine/threonine kinase status impacts cancer-associated fibroblast fate towards αSMA+ myofibroblastic (myCAF) differentiation, independently of P53 loss-of-function.
Vice versa, myCAFs foster cancer aggressiveness and specific chemoresistance patterns. Specifically, ATM deficiency is associated with the activation of reactive oxygen species and actomyosin signaling axis, increased contractility, and a greater TGF-β1 release. Pharmacological interference with TGF-β signaling reverts myofibroblast differentiation, chemoresistance, and tumor promotion in various ATM-deficient PDAC models.
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Overall, our findings demonstrate that both mouse and human HRD-PDACs reprogram their TME towards a cancer-promoting fate, making them suitable for combinatorial therapies targeting intrinsic vulnerabilities and extrinsic tumor–stroma crosstalks.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE272nnn/GSE272095 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE272095 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1135103 ncbi.nlm.nih.gov/bioproject/PRJNA1135103 ↗
project · from NCBI GEO
- PubMed 42113576 pubmed.ncbi.nlm.nih.gov/42113576 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Genome binding/occupancy profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE272095 | 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 (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: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 |