Gu Shuchen, Liu Yanjing, Zhu Bowen, Ding Ke, Yao Tso-Pang, Chen Fenfang, Zhan Lixing, Xu Pinglong, Ehrlich Marcelo, Liang Tingbo, Lin Xia, Feng Xin-Hua
From the Life Sciences Institute, and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Department of Pharmacology and Cancer Biology, Duke University Medical School, Durham, North Carolina 27710.
J Biol Chem. 2016 Mar 4;291(10):5396-405. doi: 10.1074/jbc.M115.713123. Epub 2016 Jan 13.
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 α-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 α-tubulin was correlated with epithelial morphology and it profoundly decreased during TGF-β-induced EMT. We found that TGF-β increased the activity of HDAC6, a major deacetylase of α-tubulin, without affecting its expression levels. Treatment with HDAC6 inhibitor tubacin or TGF-β type I receptor inhibitor SB431542 restored the level of acetylated α-tubulin and consequently blocked EMT. Our results demonstrate that acetylated α-tubulin can serve as a marker of EMT and that HDAC6 represents an important regulator during EMT process.
上皮-间质转化（EMT）是一个分化的上皮细胞重新编程基因表达、失去细胞连接和极性、重组细胞骨架、增加细胞运动性并呈现间质形态的过程。尽管微管（MT）在细胞骨架组织中具有关键功能，但其如何参与EMT的诱导和维持仍知之甚少。在此我们报告，在微管（MT）稳定和细胞形态中起重要作用的乙酰化α-微管蛋白可作为EMT的一种新型调节因子和标志物。高水平的乙酰化α-微管蛋白与上皮形态相关，并且在TGF-β诱导的EMT过程中其水平显著降低。我们发现，TGF-β增加了α-微管蛋白的主要去乙酰化酶HDAC6的活性，而不影响其表达水平。用HDAC6抑制剂tubacin或TGF-β I型受体抑制剂SB431542处理可恢复乙酰化α-微管蛋白的水平，从而阻断EMT。我们的结果表明，乙酰化α-微管蛋白可作为EMT的标志物，并且HDAC6是EMT过程中的一个重要调节因子。
