Our results suggest a potential axis between CX43 and SHH signalling pathway at least on two main aspects: (i) “permissive”, similarly to developmental programs in which SHH-GLI signalling favors intercellular communication and patterning that leads to microenvironmental modification and disease/tumorigenic onset; (ii) “supporting” the stemness signature of GBM, so that aberrant SHH-GLI pathway, through modified CX43-mediated subsets cellular interaction, promotes cancer stem cell population critical for GBM self-renewal. This evidence concerns the gene GLI1 and glioblastoma.