Fig. 6

DDX3X and metastasis. a In colorectal cancer, DDX3X increases the expression of KRAS by promoting SP1 binding to the KRAS promoter. In CRC harbouring mutant KRAS, DDX3X activates the KRAS/ERK/PTEN/AKT cascade to stabilize β-catenin, which then enhances ZEB1 transcription to promote metastasis. In addition, DDX3X binds with and activates CK1ε, which then phosphorylates Dvl2. Phosphorylated Dvl2 causes dissociation of PP2A and the β-catenin degradation complex, therefore stabilizing β-catenin. The accumulated β-catenin translocates into the nucleus and interacts with TCF4 to increase the expression of its downstream target genes. b In CRC harbouring wild-type KRAS, DDX3X/KRAS/HIF1-α generates a cascade feedback loop. HIF-1α binds to the YAP1 promoter to promote YAP1 transcription. YAP1 then targets PTEN by elevating miR-29c expression to activate PI3K/AKT signalling. Phosphorylated AKT activates c-fos and eventually leads to increased levels of SIX2 transcription