doi:10.1038/nindia.2009.317 Published online 26 October 2009
Colorectal cancer cells contain high levels of an active protein kinase (c-src) that help increase the invasive properties of the cells and their ability to proliferate. Researchers have now described a new means of regulation of c-src and a receptor guanylyl cyclase C, which could have important implications in the progression of colorectal cancer1.
Bacterial enterotoxins such as the heat-stable enterotoxin are one of the major causes for watery diarrhea. This toxin, produced by pathogenic strains of E. coli, as well as peptides found in the intestine called guanylin and uroguanylin, bind to and activate the receptor guanylyl cyclase C present in the colonic cell. The activated receptor makes the signaling molecule, cGMP.
Increased levels of cGMP in the cell augment fluid and ion secretion from the cell, resulting in diarrhea. Cyclic GMP also reduces the proliferation of intestinal cells by slowing down the cell cycle.
The researchers have shown that c-src phosphorylates guanylyl cyclase C, and this phosphorylation reduces cGMP production by the receptor. Consequently, activation of the receptor by guanylin or uroguanylin will no longer result in a slowing down of the cell cycle, and therefore cells can continue to multiply. They also suggest that c-src can be activated further by the phosphorylated receptor, which once again could increase the potential to form tumors in the colon.
The molecular changes that occur in a cancer cell are complex and varied, and a better understanding of some of these processes may lead to the development of effective therapeutics.