Cancer metastasis facilitated by developmental pathways: Sonic hedgehog, Notch, and bone morphogenic proteins.

This review will highlight the significance of three critical pathways in developmental biology and our emerging understanding of their roles in regulating tumor metastasis: Bone morphogenic protein (BMP), Notch and Sonic hedgehog (SHH). We will discuss parallels between their known roles in development and how these processes can be used by tumor cells to create microenvironments that enhance tumor metastasis. That tumor cells usurp pathways critical to the developing embryo is not surprising, as many of the normal developmental programs include processes that are also seen during tumor progression to a metastatic phenotype, including epithelial to mesenchymal transition (EMT), tissue specific morphogenesis, cellular motility and invasion. BMPs are involved in EMT, contribute to tissue specific morphogenesis, and are expressed in highly-metastatic tumor cells. BMPs have also been hypothesized to have a role in the establishment of a pre-neoplastic niche. Notch and SHH facilitate neovascularization, angiogenesis, EMT and can contribute to the maintenance of highly-metastatic tumor stem cells.