Requirement of HDAC6 for Transforming Growth Factor-β1-induced Epithelial-Mesenchymal Transition
作者： Bin Shan , Tso-pang Yao , Hong T. Nguyen , Ying Zhuo , Dawn R. Levy
关键词:
摘要: The aberrant expression of transforming growth factor (TGF)-β1 in the tumor microenvironment and fibrotic lesions plays a critical role progression tissue fibrosis by inducing epithelial-mesenchymal transition (EMT). EMT promotes cell motility invasiveness. How affects invasion is not well understood. Here we report that HDAC6 novel modulator TGF-β1-induced EMT. microtubule-associated deacetylase predominantly deacetylates nonhistone proteins, including α-tubulin, regulates motility. We showed accompanied HDAC6-dependent deacetylation α-tubulin. Importantly, inhibition small interfering RNA or molecule inhibitor tubacin attenuated markers, such as epithelial mesenchymal peptides, formation stress fibers. Reduced also impaired activation SMAD3 response to TGF-β1. Conversely, substantially α-tubulin markers. These findings reveal function intercepting TGF-β-SMAD3 signaling cascade. Our results identify regulator potential therapeutic target against pathological EMT, key event for fibrogenesis.
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