Extending the functions of the homeotic transcription factor Cdx2 in the digestive system through nontranscriptional activities

Core Tip

Core tip: The homeobox gene Cdx2 plays crucial functions in the gut, being the one determinant of intestinal identity during embryonic development, and then a key regulator of homeostasis of the gut epithelium throughout adulthood. It acts at the level of the stem/progenitor cells as well as in mature epithelial cells. Cdx2 is also important in digestive diseases, especially in colorectal cancer where it is thought to have a tumor suppressor role. In addition, it becomes abnormally expressed ectopically in non-intestinal organs, including gastric intestinal-type metaplasia and Barrett’s esophagus and their related adenocarcinomas, and even in leukemia. The homeoprotein Cdx2 primarily acts as a DNA-binding transcription factor. However, recent reports provide evidence for novel mechanisms of action that are transcription-independent. In this review, we summarize these new data that considerably extend the molecular potential of Cdx2 and open new questions and research area regarding the role of this homeoprotein in physiology and pathology.