High-calorie diet-induced obesity is associated with deficiency of guanylin expression and silencing of GUCY2C-signaling in colon epithelial cells, leading to tumorigenesis.
Guanylate cyclase C (GUCY2C) is a tumor-suppressing receptor silenced by loss of expression of its luminocrine hormones guanylin and uroguanylin early in colorectal carcinogenesis.
The role of GCC as a tumor suppressing receptor regulating proliferation and metabolism, together with the universal loss of guanylin and uroguanylin in tumorigenesis, suggests a model in which colorectal cancer is a paracrine hormone deficiency syndrome.