Omics · study · 2026
DNAJ-PKAc Induces Metabolic Rewiring and a Glutamine Dependency in Fibrolamellar HCC
Listed in NCBI GEO
Description
Background
Fibrolamellar carcinoma (FLC) is a pediatric and adolescent liver cancer that is characterized by a recurrent fusion of DNAJB1 and PRKACA, yielding a chimeric translated protein, DNAJ-PKAc. PRKACA encodes the catalytic subunit of protein kinase A (PKA), a regulator of cellular metabolism.
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Methods
We generated a syngeneic murine model of FLC, TIBx-DNAJ-PKAc. We utilized preclinical models of FLC and human specimens to characterize the metabolic and immune effects of DNAJ-PKAc. Results: DNAJ-PKAc induced a high glycolytic flux and glutamine dependence to support nucleotide metabolism and redox homeostasis.
TIBx-DNAJ-PKAc tumors demonstrated reduced T cell infiltration with impaired T cell activation. Systemic administration of a glutamine antagonist reversed the immune-inactivated phenotype of TIBx-DNAJ-PKAc tumors and provided durable control in combination with immune checkpoint inhibitors (ICI). Conclusion: The presence of DNAJ-PKAc creates a vulnerability to the combination of glutamine antimetabolite and ICI therapy in FLC.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE305nnn/GSE305096 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE305096 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1304424 ncbi.nlm.nih.gov/bioproject/PRJNA1304424 ↗
project · from NCBI GEO
- PubMed 41205756 pubmed.ncbi.nlm.nih.gov/41205756 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE305096 | 12 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[organism].NCBITaxon:10090 | 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 |