The anti-cancer effect of retinoic acid signaling in CRC occurs via decreased growth of ALDH+ colon cancer stem cells and increased differentiation of stem cells.

Background: Tumorigenesis is driven by stem cell (SC) overpopulation. Because ALDH is both a marker for SCs in many tissues and a key enzyme in retinoid acid (RA) signaling, we studied RA signaling in normal and malignant colonic SCs.

Hypothesis: RA signaling regulates growth and differentiation of ALDH+ colonic SCs; dysregulation of RA signaling contributes to SC overpopulation and colorectal cancer (CRC) development.

Increased Musashi-2 and Decreased NUMB Protein Levels Observed in Human Colorectal Cancer are reverted to Normal Levels by ATRA-Induced Cell Differentiation.

Background: Musashi stem cell (SC) proteins (MSI-1 & MSI-2) are known to become over expressed during colorectal tumorigenesis in humans and mice. MSI-1 overexpression induces tumorigenesis through Notch activation via inactivation of NUMB. Previous studies also show that MSI-2 overexpression in mice induces intestinal tumorigenesis but the mechanism is independent of NUMB.