Identification of a neural development gene expression signature in colon cancer stem cells reveals a role for in tumorigenesis.

Recent 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 ALDH CSCs 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) regulator to be required for tumor growth and to control expression of homebox superfamily embryonic master transcriptional regulator genes and the neural stem cell and master cell fate regulator . These data support CSCs as the source of tumor neurogenesis and suggest that targeting may provide a therapeutic differentiation strategy to eliminate CSCs and block nervous system driven disease progression.