SHH and neoplasm: While the role of somatic mutations has been extensively documented in determining tumor phenotype and many of the observed differences have been explained among different tumors [20], the biological regulation of carcinogenesis and development of tumors in the microenvironment has been extensively studied in developmental biology and our emerging understanding of their roles in regulating tumor metastasis in the view of critical signal transduction pathways: notch, bone morphogenic protein (Bmp) and sonic hedgehog (Shh).