HDAC6 is required for epidermal growth factor-induced beta-catenin nuclear localization.

Journal Article (Journal Article)

Nuclear translocation of beta-catenin is a hallmark of Wnt signaling and is associated with various cancers. In addition to the canonical Wnt pathway activated by Wnt ligands, growth factors such as epidermal growth factor (EGF) also induce beta-catenin dissociation from the adherens junction complex, translocation into the nucleus, and activation of target genes such as c-myc. Here we report that EGF-induced beta-catenin nuclear localization and activation of c-myc are dependent on the deacetylase HDAC6. We show that EGF induces HDAC6 translocation to the caveolae membrane and association with beta-catenin. HDAC6 deacetylates beta-catenin at lysine 49, a site frequently mutated in anaplastic thyroid cancer, and inhibits beta-catenin phosphorylation at serine 45. HDAC6 inactivation blocks EGF-induced beta-catenin nuclear localization and decreases c-Myc expression, leading to inhibition of tumor cell proliferation. These results suggest that EGF-induced nuclear localization of beta-catenin is regulated by HDAC6-dependent deacetylation and provide a new mechanism by which HDAC inhibitors prevent tumor growth.

Full Text

Duke Authors

Cited Authors

  • Li, Y; Zhang, X; Polakiewicz, RD; Yao, T-P; Comb, MJ

Published Date

  • May 9, 2008

Published In

Volume / Issue

  • 283 / 19

Start / End Page

  • 12686 - 12690

PubMed ID

  • 18356165

Pubmed Central ID

  • PMC3762558

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.C700185200


  • eng

Conference Location

  • United States