In a recent study using mice in which Apc (Adenomatous polyposis coli; the most frequent initial gene mutation in CRC) and the ER stress chaperone Grp78 were deleted in IECs, it could be shown that ER stress signaling results in a rapid loss of Apc mutated stem cells and self-renewal capacity through interfering with Wnt signaling (93). This evidence concerns the gene HSPA5 and colorectal carcinoma.