Although YAP binding with β-catenin and TBX5 is thought as being central to the mechanism for YAP1-mediated regulation of Wnt/β-catenin signaling [34, 36], our observations in this study identified a novel mechanism that YAP1 could confer CRC progenitor cell properties via combination with KLF5 and bound to the KLF5 binding site (GC-box) in the Ascl2 promoter induced its transcriptional activation (Figure 8D). Here, KLF5 is linked to colorectal carcinoma.