Omics · study · 2026
WDR82 suppresses breast cancer progression by inhibiting ERK-driven chemokine expression and neutrophil infiltration
Listed in NCBI GEO
Elucidating tumor-intrinsic mechanisms that drive immune evasion and shape an immunosuppressive tumor microenvironment (TME) is essential for overcoming resistance to cancer immunotherapy and developing novel therapeutic strategies.
Description
WDR82, a member of the WD-40 protein family, exhibits context-dependent regulation of cancer, yet its role in breast cancer and its influence on the immunosuppressive TME remain undefined. Here we identify WDR82 as a critical tumor suppressor that governs immune surveillance by restraining the ERK–chemokine–neutrophil axis.
WDR82 expression is downregulated in human breast cancer and correlates with poor prognosis.Using orthotopic models, we uncover a functional paradox: while Wdr82 deficiency suppresses tumor cell proliferation in vitro, it accelerates tumor growth in vivo exclusively in immunocompetent hosts, driving enhanced neutrophil infiltration and CD8⁺ T cell exhaustion. Mechanistically, WDR82 directly binds MEK1/2, disrupting c-RAF-MEK assembly and restraining ERK activation.
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Loss of Wdr82 relieves this inhibition, driving ERK-dependent production of CXCL2 and CXCL7, the key neutrophil chemoattractants that promote CXCR2-mediated recruitment. Neutrophil depletion abolishes the tumor-promoting effect of Wdr82 deficiency, confirming the functional dependency on this axis. Importantly, intratumoral delivery of WDR82-expressing adenovirus reverses neutrophil accumulation, alleviates T cell exhaustion, and suppresses tumor progression.
Our findings uncover a previously unrecognized mechanism by which WDR82 links tumor-intrinsic signaling to TME remodeling, establishing a promising therapeutic strategy for breast cancer through targeting the ERK–chemokine–neutrophil axis.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE325nnn/GSE325774 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325774 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1441595 ncbi.nlm.nih.gov/bioproject/PRJNA1441595 ↗
project · from NCBI GEO
- PubMed 42328439 pubmed.ncbi.nlm.nih.gov/42328439 ↗
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 | GSE325774 | 13 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 |