摘要：SummaryRecent evidence demonstrates that colon cancer stem cells (CSCs) can generate neurons that synapse with tumor innervating fibers required for tumorigenesis and disease progression. Greater understanding of the mechanisms that regulate CSC driven tumor neurogenesis may therefore lead to more effective treatments. RNA-sequencing analyses of ALDHPositiveCSCs from colon cancer patient-derived organoids (PDOs) and xenografts (PDXs) showed CSCs to be enriched for neural development genes. Functional analyses of genes differentially expressed in CSCs from PDO and PDX models demonstrated the neural crest stem cell (NCSC) regulatorEGR2to be required for tumor growth and to control expression of homebox superfamily embryonic master transcriptional regulatorHOXgenes and the neural stem cell and master cell fate regulatorSOX2. These data support CSCs as the source of tumor neurogenesis and suggest that targetingEGR2may provide a therapeutic differentiation strategy to eliminate CSCs and block nervous system driven disease progression.Graphical abstractDisplay OmittedHighlights•Colon cancer stem cells (CSCs) are enriched for nervous system development genes•Colon cancer cells express nerve cell markers•EGR2is required for CSC survival and tumor growth and regulatesSOX2andHOXgenes•TargetingEGR2may block cancer neurogenesis and stop disease progressionStem cells research; Cancer; Transcriptomics
