Shh is out on a limb

he association of inflammation with tumors was first noted nearly 2,000 years ago by Galen. Today, chronic inflammation caused by intestinal diseases such as colitis is known to be a major contributing factor to the onset of colon cancer. In a new report by Florian Greten, Michael Karin (University of California, San Diego, CA), and colleagues, NFB, an inflammation-inducing transcription factor, is shown to promote intestinal tumors via two pathways in two cell types. Colon cancers depend on interactions between the intestinal epithelial cells that form the tumors and white blood cells, which trigger inflammation. The authors show that a mouse model of colitis-associated colon cancer is severely reduced if NFB is inhibited in either cell type by deleting its activating kinase, IKK . If NFB was inhibited in the white blood cell lineage, epithelial tumors were less numerous and smaller because white blood cells could not induce inflammation. Proliferation of the epithelial cells was limited, probably because the dormant mutant white blood cells did not secrete growth factors. If NFB activity was blocked in intestinal epithelial cells, fewer tumors formed. The scarcity of tumors was due to increased apoptosis of the epithelial cells. NFB, possibly to help keep the intestinal epithelium intact, activates transcription of the T