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 understaneing of the mechanisms that regulate CSC driven tumor
neurogenesis may therefore lead to more effective treatments. RNA-sequencing analyses
of ALDH(Postive) 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 EGR2 to be required for tumor growth and to
control expression of homebox superfamily embryonic master transcriptional regulator
HOX genes and the neural stem cell and master cell fate regulator SOX2. These data
sur.port CSCs as the source of tumor neurogenesis and suggest that targeting EGR2
may provide a therapeutic differentiation strategy to eliminate CSCs and block nervous
system driven disease progression.
