Omics · study · 2026
Decoding SOS: eIF2B as a Key Driver of Mutant KRAS Signaling and Tumorigenesis [RNA-seq]
Listed in NCBI GEO
Beyond its established guanine exchange function (GEF) in regulating mRNA translation initiation, we demonstrate that eIF2B forms a unique complex with mutant, but not wild-type, KRAS and Son of Sevenless (SOS) in tumors, specifically when KRAS is in its active, GTP-bound state.
Description
Mechanistically, the catalytic eIF2Bε subunit binds to the allosteric RAS binding domain of SOS in complex with mutant KRAS, thereby enhancing KRAS GTP loading and activation.
The eIF2Bε subunit, SOS and mutant KRAS complex localizes to the plasma membrane (PM), where it enhances the mutant KRAS activity and MAPK pathway signaling. In parallel, the translational function of eIF2B plays a key role in the upregulation of the glycosphingolipid (GSL) pathway, thereby promoting the localization and clustering of mutant KRAS at the PM. Genetic inactivation of eIF2Bε subunit significantly reduces the growth of mutant KRAS-driven tumors in both xenograft models and an autochthonous mouse model of lung adenocarcinoma.
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Notably, increased expression of the catalytic eIF2Bε subunit correlates with poor prognosis in human cancers harboring KRAS mutations. These findings reveal a previously unrecognized link between a core component of mRNA translation machinery and oncogenic KRAS function, offering new mechanistic insight and potential therapeutic avenues in mutant KRAS-driven malignancies.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE304nnn/GSE304640 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE304640 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1301973 ncbi.nlm.nih.gov/bioproject/PRJNA1301973 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- RNA sequencing 65%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE304640 | 12 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| 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 (65%) |
| 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 |