title: Loss of α-Tubulin Acetylation Is Associated with TGF-β-induced Epithelial-Mesenchymal Transition.
abstract: 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.
authors.affiliation: From the Life Sciences Institute, and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Shuchen
authors.initials: S
authors.lastname: Gu
authors.affiliation: From the Life Sciences Institute, and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Yanjing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: From the Life Sciences Institute, and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Bowen
authors.initials: B
authors.lastname: Zhu
authors.affiliation: From the Life Sciences Institute, and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Ding
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical School, Durham, North Carolina 27710.
authors.forename: Tso-Pang
authors.initials: TP
authors.lastname: Yao
authors.affiliation: From the Life Sciences Institute, and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Fenfang
authors.initials: F
authors.lastname: Chen
authors.affiliation: Institute of Nutritional Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Lixing
authors.initials: L
authors.lastname: Zhan
authors.affiliation: From the Life Sciences Institute, and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Pinglong
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of Cell Research and Immunology, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Ehrlich
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery and the Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, School of Medicine Zhejiang University, Hangzhou, Zhejiang 310009, China, and.
authors.forename: Tingbo
authors.initials: T
authors.lastname: Liang
authors.affiliation: From the Life Sciences Institute, and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Lin
authors.affiliation: From the Life Sciences Institute, and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China, Michael E. DeBakey Department of Surgery, and Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas 77030 xhfeng@zju.edu.cn xfeng@bcm.edu.
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Feng
mesh_terms: D000107:Acetylation; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D004149:Dioxoles / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition; D057809:HEK293 Cells; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D061986:MCF-7 Cells; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism*
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D000813:Anilides; D001549:Benzamides; D004149:Dioxoles; D006877:Hydroxamic Acids; D016212:Transforming Growth Factor beta; D014404:Tubulin; C474316:tubacin; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases
keywords: acetylation; epithelial-mesenchymal transition (EMT); histone deacetylase 6 (HDAC6); microtubule; transforming growth factor β (TGF-β)