6533b85dfe1ef96bd12be7ca

RESEARCH PRODUCT

STEM CELLS AND COLON CANCER

subject

description

The current concept of tumorigenesis suggests that cancers arise and are “driven” by cells with stem cell-like properties, known as cancer stem cells (CSCs), which share many functional and molecular features with normal stem cells. Self-renewal key pathways (e.g., Wnt, Notch, and Hedgehog) are tightly regulated in normal stem cells, but are impaired in CSCs. For instance, active Wnt pathway plays a crucial role in colon cancer pathophysiology, where deregulation of the adenomatous polyposis coli (APC) gene, a negative regulator of Wnt signaling, represents one of the earliest alterations in the multistep process of colon carcinogenesis, causing early adenoma formation. Normal colon stem cells reside at the base of the crypts, in specialized regions termed “niches,” that provide a microenvironment structured to ensure their self-renewal. It is becoming increasingly clear that CSCs are involved in tumor recurrence and resistance to conventional therapies, due to high expression levels of ATP-binding cassette (ABC) transporters, slow cycling rates, and the presence of cytoprotective factors. Future therapeutic strategies should selectively target CSCs for a complete clinical remission. Keywords: Stem cell; Colon cancer stem cell; Crypt; Niche