Protection against anoikis and down-regulation of cadherin expression by a regulatable beta-catenin protein

J Biol Chem. 2002 May 24;277(21):18677-86. doi: 10.1074/jbc.M105331200. Epub 2002 Mar 19.


beta-Catenin signaling plays a key role in a variety of cellular contexts during embryonic development and tissue differentiation. Aberrant beta-catenin signaling has also been implicated in promoting human colorectal carcinomas as well as a variety of other cancers. To study the molecular and cellular biological functions of beta-catenin in a controlled fashion, we created a regulatable form of activated beta-catenin by fusion to a modified estrogen receptor (ER) ligand binding domain (G525R). Transfection of tissue culture cells with expression vectors encoding this hybrid protein allows the signal transduction function of beta-catenin to be induced by the synthetic estrogen, 4-hydroxytamoxifen, leading to regulated activation of a beta-catenin-lymphocyte enhancer-binding factor-dependent reporter gene as well as induction of endogenous cyclin D1 expression. The activation of ER-beta-catenin signaling rescues RK3E cells from anoikis and correlates with an increased phosphorylation of mitogen-activated protein kinase. The inhibition of anoikis by ER-beta-catenin can be abolished by a mitogen-activated protein kinase pathway inhibitor, PD98059. Evidence is also provided to show that ER-beta-catenin down-regulates cadherin protein levels. These findings support a key role for activated beta-catenin signaling in processes that contribute to tumor formation and progression.

MeSH terms

  • Animals
  • Anoikis*
  • Cadherins / metabolism*
  • Cell Line
  • Cytoskeletal Proteins / metabolism
  • Cytoskeletal Proteins / physiology
  • Dogs
  • Down-Regulation / physiology*
  • Gene Expression Regulation / physiology
  • Genes, Reporter
  • MAP Kinase Signaling System
  • Mutagenesis, Site-Directed
  • Trans-Activators*
  • beta Catenin


  • Cadherins
  • Cytoskeletal Proteins
  • Trans-Activators
  • beta Catenin