Study Sheds Light on Signaling Mechanism in Stem Cells, Cancer

By Jennifer O'Brien, UCSF News Services | October 24, 2005

UCSF scientists have illuminated a key step in a signaling pathway that helps orchestrate embryonic development. The finding, they say, could lead to insights into the development of stem cells, as well as birth defects and cancers, and thus fuel therapeutic strategies.

The study, reported in Nature (Oct. 13, 2005), focuses on the Hedgehog family of signaling molecules, which play a central role in directing development of the early embryo's growth and spatial plan, as well as its later organ and limb development. Defects in Hedgehog signaling are a significant cause of some birth defects and cancers.

Secreted from one cell, a Hedgehog signal shoots to the surface receptor of a second cell, and then, in a rapid-fire succession of biochemical reactions, relays a message into the cell's nucleus. There, it issues an instruction, prompting the cell to divide, or specialize into a particular cell type, or migrate to help form another part of the embryo, and so on. This transaction, known as signal transduction, is a ceaseless activity of embryonic development.

Scientists have long known that Hedgehog signaling requires the activity of a protein known as Smoothened. This has been demonstrated in animals ranging from insects to humans.

They have also known that defects in Smoothened, which only functions within Hedgehog signaling, are responsible for some cases of human cancers -- most prominently a skin cancer known as basal cell carcinoma and a childhood brain cancer known as medulloblastoma -- as well as some birth defects.

However, they have not known how Smoothened executes its function, nor where it is located in the target cell.

Read more at Jennifer O'Brien, UCSF News Services