Loss of α-Tubulin Acetylation Is Associated with TGF-β-induced Epithelial-Mesenchymal Transition

The epithelial-to-mesenchymal transition (EMT) is a process by which differentiated epithelial cells reprogram gene expression, lose their junctions and polarity, reorganize their cytoskeleton, increase cell motility and assume a mesenchymal morphology. Despite the critical functions of the microtubule (MT) in cytoskeletal organization, how it participates in EMT induction and maintenance remains poorly understood. Here we report that acetylated -tubulin, which plays an important role in microtubule (MT) stabilization and cell morphology, can serve as a novel regulator and marker of EMT. A high level of acetylated -tubulin was correlated with epithelial morphology and it profoundly decreased during TGF--induced EMT. We found that TGF- increased the activity of HDAC6, a major deacetylase of -tubulin, without affecting its expression levels. Treatment with HDAC6 inhibitor tubacin or TGF- type I receptor inhibitor SB431542 restored the level of acetylated -tubulin and consequently blocked EMT. Our results demonstrate that acetylated -tubulin can serve as a marker of EMT and that HDAC6 represents an important regulator during EMT process.