Omics · study · 2026
SCD1 and SCD5 Modulate PARP-Dependent DNA Repair via Fatty Acid Desaturation in Glioblastoma
Listed in NCBI GEO
Glioblastoma (GBM) relies on fatty acid metabolism to sustain its aggressive growth.
Description
While the role of stearoyl-CoA desaturase-1 (SCD1) in GBM is established, the function of its brain-enriched isoform, SCD5, remains unexplored. Here, we demonstrate that SCD5 is essential for glioblastoma stem cell (GSC) maintenance and genomic stability, with elevated expression in GSCs that declines upon differentiation, underscoring its role in tumor initiation.
Through shotgun lipidomics, 13C metabolic flux analysis, and functional genomics, we reveal that SCD1 and SCD5 play non-redundant roles in fatty acid desaturation, with SCD5 preferentially desaturating C18:0 and uniquely contributing to sphingolipid remodeling. Genetic silencing of either isoform disrupts cell cycle progression, impairs DNA damage repair, and reduces GSC viability, while SCD5 knockdown significantly extends survival in orthotopic GBM models.
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Mechanistically, loss of SCD activity or saturated fatty acid accumulation triggers PARP1 hyperactivation and subsequent degradation, depleting RAD51 to compromise homologous recombination and induce parthanatos. These findings uncover a lipid-mediated vulnerability in GBM, linking fatty acid desaturation to PARP1-dependent genome integrity. Targeting SCD5 may offer a novel therapeutic strategy to eliminate therapy-resistant GSCs and enhance the efficacy of genotoxic or immunotherapeutic interventions.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE316nnn/GSE316537 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE316537 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1403278 ncbi.nlm.nih.gov/bioproject/PRJNA1403278 ↗
project · from NCBI GEO
- PubMed 41979920 pubmed.ncbi.nlm.nih.gov/41979920 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Cancer 65%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE316537 | 14 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 (65%) |
| 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 |