Tankyrase inhibitors target colorectal cancer stem cells via AXIN-dependent downregulation of c-KIT tyrosine kinase

Tankyrase, a poly(ADP-ribose) polymerase family member, destabilizes Axin and positively regulates the Wnt/β-catenin signaling. We demonstrated that tankyrase inhibitors can target the colorectal cancer stem-like cells. Tankyrase inhibitors efficiently suppress colorectal cancer stem-like cell proliferation via AXIN-dependent manner. We sorted CD44-positive COLO-320DM cells, which showed a characteristic of CSCs and were targeted by tankyrase inhibitors. We analyzed gene expression profile of CD44-positive cells (CD44-positive 01, 02, 03) and CD44-negative cells (CD44-negative 01, 02, 03). We sorted CD44-positive and -negative COLO-320DM cells and found a tankyrase inhibitors can selectively target the CD44-positive COLO-320DM cells. We compared gene expression between CD44-positive (CD44-positive cells 01, 02, 03) and CD44-negative (CD44-negative 01, 02, 03) cells.