Excel · study · 2026
Endothelial exosomes remodel chromatin accessibility and superenhancer in cancer cells to promote liver metastatic colonization
Listed in NCBI GEO
Liver-organotropic metastasis occurs in cancers such as uveal melanoma (UM) and pancreatic ductal adenocarcinoma (PDAC) and is a leading cause of mortality at the terminal stage.
Description
Colonization is a rate-limiting and converging step in the metastatic cascade. The drivers underlying liver colonization have largely remained elusive.
In this report, we hypothesized that pioneer transcription factors (TFs) increase chromatin accessibility and SE remodeling, which subsequently promote colonization-associated cellular features (e.g., proliferation, survival, cancer stem cells (CSCs), motility) by driving the transcription of the respective SE-associated genes. We tested this hypothesis and discovered that the pioneer TF KLF4 promoted chromatin accessibility and SE remodeling by ATAC-seq and ChIP-seq.
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Chromatin accessibility and SE remodeling significantly increased the transcription of the SE-associated genes MCL-1 and RASGRP3, which consequently promoted proliferation, motility, and metastasis. Furthermore, the upregulation of KLF4 expression in UM cells was promoted by RN7SL2-containing exosomes from surrounding endothelial cells. Analysis of clinical datasets revealed that the overexpression of RIG-I, STAT1, KLF4 and RASGRP3 was individually correlated with shorter metastasis-free survival or overall survival in patients with UM and PDAC.
In conclusion, the identification of the exoRN7SL2-STAT1-KLF4-SEs-RASGRP3 signaling axis may help elucidate metastatic colonization through interactions between tumor cells and the endothelial niche and may yield novel and viable therapeutic targets.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE329nnn/GSE329420 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE329420 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1458847 ncbi.nlm.nih.gov/bioproject/PRJNA1458847 ↗
project · 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 | GSE329420 | 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: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 |