Omics · study · 2026
GADD45A links Hippo-TEAD signaling to estrogen response and luminal identity in HR-positive breast cancer
Listed in NCBI GEO
Growth arrest and DNA damage-inducible alpha (GADD45A) has context-dependent roles in cancer, yet its function in hormone receptor-positive (HR+) breast cancer remains poorly defined.
Description
We characterized GADD45A across breast cancer subtypes and investigated its prognostic significance and connection to estrogen and Hippo-TEAD signaling in HR+HER2− breast cancer. GADD45A protein expression was evaluated by immunohistochemistry in 100 tissue microarray samples and 16 CDK4/6 inhibitor-treated metastatic cases.
Prognostic associations were assessed in the METABRIC (n = 1,904) and TCGA-BRCA cohorts. siRNA-mediated GADD45A knockdown was performed in MCF7 and T47D cells followed by RNA sequencing and integration with TEAD4 ChIP-seq data. GADD45A protein was preferentially expressed in HR+HER2− tumors and correlated with estrogen receptor levels. High GADD45A expression was associated with improved overall and relapse-free survival in HR+HER2− breast cancer but not in other subtypes.
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GADD45A knockdown led to downregulation of estrogen response and Hippo-TEAD positive effector programs with concurrent upregulation of E2F targets and cell cycle pathways. Integration with TEAD4 ChIP-seq data demonstrated significant enrichment of TEAD4 promoter binding among GADD45A-regulated genes, including Hippo-TEAD components, chromatin remodeling machinery, and luminal identity regulators. GADD45A is a subtype-specific prognostic marker in HR+HER2− breast cancer that sustains estrogen-responsive and TEAD-mediated transcriptional programs, identifying it as a previously unrecognized link between Hippo-TEAD signaling and luminal gene maintenance.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE323nnn/GSE323399 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE323399 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1428490 ncbi.nlm.nih.gov/bioproject/PRJNA1428490 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75% · RNA sequencing 75% · Sequencing 75%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE323399 | 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[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| 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 |