In fact, de novo mutational activation of Shh pathway by itself can result in cancer [49], and it is also involved in the synergy of cancer and stromal cells, as stromal hh production stimulates neoplastic proliferation and metastasis [50], and tumour-secreted hh ligands in turn induce CAF transformation generating a tumour-promoting microenvironment [51]. Here, SHH is linked to neoplasm.