Regulation of epithelial-mesenchymal transition and metastasis by TGF-β, P-bodies, and autophagy.

Processing bodies (P-bodies) are ribonucleoprotein complexes involved in post-transcriptional mRNA metabolism that accumulate in cells exposed to various stress stimuli. The treatment of mammary epithelial cells with transforming growth factor-beta (TGF-β), triggers epithelial-mesenchymal transition (EMT), and induces the formation of P-bodies. Ectopic expression of the transcription factor TWIST, which stimulates EMT downstream of the TGF-β receptor, also promotes P-body formation. Removal of TGF-β from treated cells results in the clearance of P-bodies by a process that is blocked by inhibitors of autophagy. Activators of autophagy enhance P-body clearance and block EMT. Blockage of P-body formation by disruption of the gene for DDX6, a protein essential for P-body assembly, blocks EMT and prevents tumor cell metastasis