{"database":"GEO","file_versions":[],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE300573"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"ETS1 Orchestrates a Hybrid EMT Program Driving in vivo Metastasis and Immune Evasion","description":"Transcriptional Intratumoral heterogeneity (ITH) is a hallmark of aggressive cancers, yet how transcriptional ITH programs drive tumor metastasis and immune evasion in upper aerodigestive squamous cell carcinoma (UASCC) remains unclear. Through single-cell RNA sequencing analysis of UASCC cells and patient tumors, we uncovered a hybrid EMT (hEMT) ITH program linked to metastatic dissemination. The transcription factor ETS1 was identified as a master regulator of hEMT program, directly activating pro-metastatic genes and promoting distant spread in vivo. Unexpectedly, ETS1 also orchestrated an immune-cold tumor microenvironment by transcriptionally activating the STAT1-PDL1 axis, suppressing T lymphocyte infiltration and elevating immune checkpoint molecules. Clinically, ETS1-high tumors strongly correlated with poor survival and resistance to immune checkpoint blockade across multiple cohorts. Leveraging drug screens, we discovered that ETS1-high cancers are vulnerable to HSP90 inhibitors (e.g., Alvespimycin), which suppress ETS1 by disrupting HIF1A-mediated transcriptional activation. Together, our work reveals ETS1 as a dual driver of tumor distal metastasis and immune evasion in UASCC, while nominating HSP90 inhibition as a tailored strategy for ETS1-driven tumors. These findings provide a roadmap for targeting aggressive ITH subsets and overcoming immunotherapy resistance.","dates":{"publication":"2026/05/08"},"accession":"GSE300573","cross_references":{"GSM":["GSM9064727","GSM9064728","GSM9064725","GSM9064726"],"GPL":["24676"],"GSE":["300573"],"taxon":["Homo sapiens"]}}