Excel · study · 2026
Targeting the calcium-activated K+ channel KCa3.1 in pancreatic ductal adenocarcinoma
Listed in NCBI GEO
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal forms of cancer, distinguished by its dense desmoplastic microenvironment and the scarcity of therapeutic options.
Description
Recent studies have identified the calcium-activated potassium channel KCa3.1 as a potential therapeutic target in oncology. There is a correlation between increased KCa3.1 expression and poor overall survival of PDAC patients.
Therefore, we investigated the therapeutic potential of KCa3.1 targeting in PDAC using TRAM-34 and maurotoxin alone or in combination with gemcitabine. We utilized the KPfC (Kraswt/LSL–G12D Tp53fl/+ Pdx1-Cre) mouse model to evaluate the in vivo therapeutic efficacy of KCa3.1 inhibition. We developed a three-dimensional mixed spheroid model co-culturing pancreatic cancer cells and pancreatic stellate cells (PSCs) to mimic the tumor microenvironment.
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To gain mechanistic insights, we performed RNA sequencing on mixed spheroids containing KCa3.1 CRISPR knockout pancreatic cancer cells and explored the functional impact of KCa3.1 targeting in the spheroid model. In vivo, KCa3.1 inhibition led to a decrease in tumor growth without inducing excessive fibrosis. KCa3.1 inhibition was associated with increased cell death and diminished epithelial-mesenchymal transition (EMT).
In vitro inhibition of the plasma membrane KCa3.1 channel by maurotoxin resulted in decreased invasive potential and increased cell death. These effects can mechanistically account for the therapeutic benefits of targeting KCa3.1 channels in PDAC.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE279nnn/GSE279207 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE279207 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1171377 ncbi.nlm.nih.gov/bioproject/PRJNA1171377 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75% · RNA sequencing 75% · Sequencing 75%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE279207 | 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[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| 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 |