SHH and neoplasm: Single SOX2+ tumor cells or clusters of SOX2+ tumor cells are largely distributed in the tumor and could promote the proliferation and the invasion of the surrounding “non-mutated” epithelial cells by the overexpression of growth factors (vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), fibroblast growth factor (FGF), and transforming growth factor beta (TGF-beta)), and cytokines (such as sonic hedgehog or SHH) [42,44].