GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE284nnn/GSE284443/primaryOK200TranscriptomicsMus musculus Homo sapiens Genome binding/occupancy profiling by high throughput sequencingExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE284443GEOGSEfalseL1CAM generates SOX2+ metastatic progenitors through planar cell polarity signaling in lung adenocarcinomaLung adenocarcinoma (LUAD) is a leading cause of cancer-related deaths worldwide, with most fatalities attributed to metastasis. A primitive SOX2+ progenitor state, rare in primary tumors, becomes prominent in LUAD metastatic lesions and exhibits metastasis-initiating capacity. The signals that determine the emergence of SOX2+ progenitors are unknown. We report that the cell adhesion molecule L1CAM, a marker of metastasis-initiating regenerative progenitors, plays a crucial role in the emergence of LUAD SOX2+ progenitors. Mechanistically, L1CAM induces the planar cell polarity (PCP) complex to activate c-Jun, which in turn interacts with the chromodomain helicase CHD1 to drive Sox2 transcription and generate metastasis-initiating regenerative progenitors. Treatment with an L1CAM antibody drug conjugate (ADC) effectively eliminates these LUAD cells and eradicates patient-derived xenograft metastases. Our findings identify L1CAM/PCP signaling as a driver of the SOX2+ LUAD metastatic progenitor state and provide an approach to treating metastasis by targeting L1CAM+ LUAD progenitors.2026/04/16GSE284443GSM8684424GSM8684423GSM8684426GSM8684425GSM8684428GSM86844272467624247284443Mus musculus Homo sapiens