Fig. 4. TCF/LEF function in intestine and colorectal cancer. The stem cell population at the base of the crypt in the intestine produces a proliferating progenitor cell population that migrates up the side of the crypt. Upon reaching the crypt-villus junction, cells begin to differentiate and continue moving up the villus until mature cells are shed into the lumen at the tip of the villus. The levels of nuclear -catenin, and therefore active TCF/LEF, are highest at the base of the crypt in the stem cell and proliferating progenitor population. In this population it is proposed that full-length TCF-4 (activating, green) and NTCF-1 (repressing, red) are the main active TCF/LEFs. However, when mutated Wnt signalling leads to colorectal cancer, ectopic expression of full-length LEF-1 is readily detected. As a result the predominant TCF/LEF isoforms present in colorectal cancer are activating (green) as opposed to repressive (red) TCF/LEFs. The levels of nuclear -catenin in colorectal cancer are very high because Wnt signalling pathway mutations mean that -catenin cannot be degraded. Figure modified from Radtke and Clevers (Radtke and Clevers, 2005).