Figure 3.

The paradoxical HH pathway. SHH, secreted by tumour-associated astrocytes, induces nestin expression in tumour cells lacking PTCH1, through a signalling mechanism that requires SMO. Nestin accumulates in tumour cells and binds to GLI3, thereby abrogating a negative feedback loop, leading to increased HH pathway activity. Both the induction of GLI1 expression in the absence of PTCH1 and SHH-induced nestin expression require the presence of cholesterol. Statins and vismodegib synergize in the inhibition of HH pathway activity.