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The p68 RNA helicase is a prototypical DEAD box family ofRNA helicase, whose cellular function is to modulate dynamic RNA structures and complex RNA-protein interactions.P68 RNA helicase plays very important roles in cell proliferation and organ maturation.We report here that p68 RNA helicase is phosphorylated at multiple amino acid residues.Tyrosyl phosphorylation of p68 is associated with cancer progression and metastasis.Phosphorylation at Y593 mediates PDGF stimulated Epithelial-Mesenchymal-Transition (EMT) by facilitating beta-catenin nuclear localization via a Wnt-independent pathway.The phosphor-p68 facilitates beta-catenin nuclear translocation by blocking phosphorylation of beta-catenin by GSK-3beta and displacing Axin from beta-catenin, Moreover, our experiments further show that p68 shuttles between the nucleus and the cytoplasm.The shuttling activity of p68 enables p68 transport cytoplasmic beta-catenin to the nucleus.Experiments in our laboratory also demonstrate that phosphorylation of p68 promotes EMT and cancer metastasis by upregulating Snail expression.The phosphor-p68 up-regulates Snail gene transcription by displace HDAC 1 from Mi-2/NuRD chromatin remodeling complex at the promoter.Interestingly, phosphorylation of p68 RNA helicase turns an RNA helicase to a protein displacer.Our experimental results showed that p68 RNA helicase acquires a protein substrate dependent ATPase activity after phosphorylation.Our observations suggest an interesting model.A DEAD box RNA helicase can function as a protein displacer that modulates important protein-protein interactions in bio-macromolecular complex, which regulates the assembly/disassembly of molecular machines in various biological processes.