GUCY2C and colorectal cancer: Together, these observations suggest that GC-C is a lineage-specific tumor suppressor normally involved in the spatiotemporal patterning of the intestinal crypt-villus axis whose silencing, reflecting loss of expression of paracrine hormones, corrupts downstream processes universally underlying neoplastic transformation [87,89,100,110,115,116,117] Accordingly, colorectal tumorigenesis regulated by GC-C signaling suggests a novel pathophysiological paradigm in which colorectal cancer initiates, in part, as a disease of paracrine hormone insufficiency.