Omics · study · 2026
Hippuric Acid Suppresses Triple-Negative Breast Cancer via the EGFL8-Notch Signaling Axis
Listed in NCBI GEO
Triple-negative breast cancer (TNBC) remains a highly aggressive malignancy with limited therapeutic options due to the absence of well-defined molecular targets.
Description
Diet-induced obesity (DIO) promotes TNBC progression by reshaping systemic metabolism and inflammatory responses; however, the key circulating metabolites involved and their mechanisms remain largely unclear. This study aimed to identify key metabolites associated with TNBC progression and further investigate their biological functions and molecular mechanisms.
Targeted metabolomics profiling was performed on serum samples from MMTV-PyMT spontaneous breast cancer mice to identify differential metabolites associated with DIO. Hippuric acid was identified as a significantly altered metabolite under DIO conditions. Functional studies demonstrated that hippuric acid markedly inhibited the proliferation, migration, and invasion of TNBC cells, with minimal effects on non-TNBC cells.
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Transcriptomic analysis identified EGFL8 as a potential downstream target, which was further confirmed by qPCR and functional assays. Overexpression of EGFL8 suppressed malignant phenotypes, whereas its knockdown promoted tumor progression. Rescue experiments showed that EGFL8 partially mitigated the inhibitory effects of hippuric acid on TNBC, suggesting that it functions as an important mediator in this process.
Mechanistically, hippuric acid exerted its anti-tumor effects at least in part through modulation of the EGFL8–Notch signaling axis. In conclusion, hippuric acid suppresses TNBC progression via the EGFL8-Notch signaling pathway. These findings highlight a previously unrecognized role of a gut microbiota-derived metabolite in TNBC and suggest its potential as a therapeutic candidate, providing new prospective targets and a theoretical basis for metabolic intervention for TNBC.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE334nnn/GSE334662 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE334662 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1476123 ncbi.nlm.nih.gov/bioproject/PRJNA1476123 ↗
project · from NCBI GEO
- PubMed 42351828 pubmed.ncbi.nlm.nih.gov/42351828 ↗
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 | GSE334662 | 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 (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 |