{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE325nnn/GSE325774/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325774"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"WDR82 suppresses breast cancer progression by inhibiting ERK-driven chemokine expression and neutrophil infiltration","description":"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. 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. 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.","dates":{"publication":"2026/06/25"},"accession":"GSE325774","cross_references":{"GSM":["GSM9613183","GSM9613184","GSM9613185","GSM9613186","GSM9613180","GSM9613181","GSM9613182","GSM9613178","GSM9613179"],"GPL":["17021"],"GSE":["325774"],"taxon":["Mus musculus"],"PMID":["[42328439]"]}}