GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE316nnn/GSE316156/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE316156GEOGSEfalseLoss of Sox10 prevents tumor initiation in vivo and induces luminal-to-basal reprogramming in Neu+ tumor cellsThe SRY-HMG-Box transcription factor SOX10 plays a critical role in neural crest development, but its function in epithelial tumorigenesis remains unclear. Here, we identify SOX10 as a key regulator of tumor-initiating activity in Neu-driven mammary cancers. Genetic ablation of Sox10 in the luminal compartment of MMTV-Neu (NIC) mice resulted in delayed but normal mammary gland development. Sox10 deletion conferred a dose-dependent delay in tumor onset, with a complete loss of tumor initiation in Sox10-deficient luminal cells. CRISPR/Cas9-mediated Sox10 inactivation in Neu-transformed tumor cells led to reduced 3D invasion and diminished self-renewal in mammosphere assays. Established Sox10-null cell lines exhibited markedly impaired growth in orthotopic transplant models and failed to colonize lung tissue following tail vein injection, suggesting a loss of tumor-initiating capacity. Transcriptomic profiling revealed that Sox10-deficiency in Neu+ tumor cells induces a luminal-to-basal/stem-like shift and the downregulation of several genes associated with genetic networks regulating stemness. Collectively, these findings demonstrate that Sox10 is required for a permissive cell progenitor state for Neu-driven tumor initiation and that it is critical to sustain the invasive and self-renewing traits that drive tumor progression and metastasis.2026/08/05GSE316156GSM9445947GSM9445946GSM9445952GSM9445951GSM9445954GSM9445953GSM9445950GSM9445949GSM944594824247316156Mus musculus