ABSTRACT
This chapter discusses the signals that drive the continuous cycling and trigger the terminal differentiation and suicide of skin keratinocytes. It provides a model of the signals that might drive the proliferation and trigger the terminal differentiation of colon cells. The chapter shows how these signals become increasingly unnecessary and ineffective during the neoplastic transformation of hepatocytes, keratinocytes, and colon cells. Dietary calcium opposes colon tumor promotion by binding to, and thus inactivating, the cell-killing free fatty acids and secondary bile acids, while vitamin D inhibits the compensatory proliferative response of the crypt cells to the loss of mucosal cells. The proliferative activity in the crypts of the colon as well as the small intestine is tightly regulated by a negative feedback mechanism that responds to changes in mucosal cellularity. The mature, differentiated, and aging cells eventually debouch onto the mucosal plain and march toward the extrusion zones where they may be programmed to commit suicide by apoptosis.
