Omics · study · 2026
Complex I Drives Glutamine-Dependent TCA Cycle to Support Viability of MYChigh Breast Cancer Cells
Listed in NCBI GEO
In many cancers, stably elevated MYC levels drive persistent and concerted activation of cell growth promoting anabolic programs and cell cycle in ways distinct from normal cells.
Description
Therefore, synthetic-lethal targeting of MYC-reprogrammed pathways offers selective strategies against MYChigh tumors. This study identifies enhanced mitochondrial respiration as a hallmark of MYC overexpressing cancer cells.
Mitochondrial respiration sustains TCA cycle by regenerating NAD+ through complex I-mediated oxidation of NADH. Metabolic carbon tracing analysis reveals that MYC shifts TCA cycle carbon source from glucose to glutamine. Inhibition of the glutamine-fueled TCA cycle using NAD+-depleting complex I inhibitors promotes MYC-dependent synthetic lethality in breast cancer cells.
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In mouse models of MYChigh tumors, persistent inhibition of tumor growth is achieved through combined inhibition of complex I and glutaminolysis. Altogether, the high respiration rate observed in MYChigh cells supports a glutamine carbon-enriched TCA cycle rendering MYChigh tumors selectively vulnerable to inhibitors of mitochondrial respiration and glutaminolysis. This deposition specifically contains the RNA-sequencing data generated from the breast cancer cell lines described in the study.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE331nnn/GSE331349 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE331349 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1467718 ncbi.nlm.nih.gov/bioproject/PRJNA1467718 ↗
project · from NCBI GEO
- PubMed 42397738 pubmed.ncbi.nlm.nih.gov/42397738 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE331349 | 15 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: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 |