Omics · study · 2026
Pleckstrin-2 Promotes Cutaneous Squamous Cell Carcinoma by Recruiting Profilin-1 to the Membrane to Destabilize Cytosolic PTEN
Listed in NCBI GEO
Cutaneous squamous cell carcinoma (cSCC) is a prevalent skin malignancy driven by ultraviolet-induced genomic damage, and advanced disease remains clinically challenging due to limited therapeutic options.
Description
Through integrative transcriptomic and functional analyses, we identify Pleckstrin-2 (PLEK2) as a previously unrecognized oncogenic driver in cSCC. PLEK2 is markedly upregulated in patient tumors, cSCC cell lines, and UV-induced mouse models.
Genetic perturbation studies demonstrate that PLEK2 promotes proliferation, migration, epithelial–mesenchymal transition, and tumorigenicity. Mechanistically, PLEK2 recruits Profilin-1 (PFN1) to the plasma membrane through its DEP domain, thereby reducing cytosolic PFN1 pool required for PTEN stabilization. This PFN1 sequestration accelerates PTEN polyubiquitination and degradation, thereby sustaining AKT pathway activation.
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Upstream, we identify ETS2 as a direct transcriptional activator of PLEK2, establishing an ETS2–PLEK2–PFN1–PTEN axis that drives cSCC progression. These findings delineate a signaling pathway regulating PTEN stability and AKT activation, and provide mechanistic insight into cSCC progression.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE341nnn/GSE341811 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE341811 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1379907 ncbi.nlm.nih.gov/bioproject/PRJNA1379907 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Disease 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE341811 | 12 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:disease | 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[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 |