Fig. 2. Hh signaling in the cancer and stromal cells.

In the cancer cell, Shh expression is induced by Kras and NFkB pathways. As a result, Shh can either activate Hh signaling in the cancer cell or the stromal cell, through canonical Hh signaling. In addition, other signaling pathways, such as Kras, can also induce Gli transcriptional activity (non-canonical Hh signaling) in the tumor compartment. As a result of Hh signaling activation, cancer cells will be more proliferative, more invasive and more resistant to apoptosis. Conversely, Hh signaling activation in the stromal cells can feedback to stimulate cancer cell proliferation.