Wnt signaling in colon cancer stem cells

Colorectal cancer is the second leading cause of cancer-related death in the United States. Among many gene mutations associated with colorectal cancer, mutation of APC (adenomatous polyposis coli) or β-catenin, which activates Wnt signaling, represents the initiation step of colon tumorigenesis. Wnt signaling is known to play multiple roles in early development and formation of human cancers. In addition, Wnt signaling also regulates the self-renewal and differentiation of adult stem cells. Recently, cancer stem cells have emerged as an exciting new concept in cancer research. However, many challenging questions have also arisen. What is the definition of a cancer stem cell? Where do such cells originate and what are the markers for these cells? What's the genetic and epigenetic machinery that regulate the homeostasis of this cell population? What is the mechanism underlying the process of cancer stem cell-involved tumorigenesis? In this review, we will discuss the development and trends in the field of cancer stem cell research, with emphasis on colon cancer stem cells. Since Wnt signaling is involved in both intestinal stem cells and colon cancers, we will first discuss the mechanisms of the Wnt signal transduction pathway, and then discuss the roles of Wnt signaling in normal intestine and in colon cancer. Finally, we will discuss the challenges and opportunities in colon cancer stem cell research.