Stem cells and colorectal cancerogenesis: new insight

Intestinal stem cells are monoclonal, multipotent cells residing in the niches of intestinal cripts where they regulate colonic epithelial turnover. It has been recently demonstrated that alterations in signalling transduction of the intestinal stem cells is implicated in the onset of colorectal cancer. Chronic inflammation may be one of the mechanisms involved in cancerogenesis because failure of resident stem cells in repairing the epithelial damage for the chronic insult, recruits bone marrow stem cells, which can develop genetic mutations due to the inflamed environment, leading to cancer. The main mutations associated with colorectal cancer affect the most important cellular signalling pathway, the Wnt. Mutations of adenomatous polyposis coli (APC) tumor suppressor gene and β catenin oncogene are the most common and severe alterations of this pathway. Tissue invasion and metastatization require a two-side transition of cancer stem cells, from epithelial phenotypes to mesenchimal one (epithelial transition tumor, EMT) and from the mesenchimal phenotype to the epithelial one (mesenchymal transition tumor, MET) under the regulatory effects of the environment, the intracellular β catenin distribution and Pl6 cell cycle inhibitor. Stem cells provide normal intestinal epithelial turnover, but may also promote intestinal cancerogenesis, and, since the cancer stem cells during the mesenchimal status are resistant to the chemotherapy (which is active only on proliferating cells), they represent the true target of future therapeutic approaches in oncology.