Cross-regulation of beta-catenin-LEF/TCF and retinoid signaling pathways

Curr Biol. 1999 Dec 2;9(23):1415-8. doi: 10.1016/s0960-9822(00)80088-3.


Vitamin A derivatives (retinoids) are potent regulators of embryogenesis, cell proliferation, epithelial cell differentiation and carcinogenesis [1]. In breast cancer cells, the effects of retinoids are associated with changes in the cadherin-beta-catenin adhesion and signaling system [2] [3]. beta-catenin is a component of the Wnt signaling pathway, which regulates several developmental pathways [4]. Increases in cytoplasmic beta-catenin and beta-catenin signaling are also associated with numerous cancers, and are particularly important in colon cancer [5]. The oncogenic and developmental effects of beta-catenin are mediated by its interaction with and activation of members of the LEF/TCF family of transcription factors [6] [7] [8]. Here, we shown that retinoic acid (RA) decreases the activity of the beta-catenin-LEF/TCF signaling pathway. This activity of RA was independent of the adenomatous polyposis coli (APC) tumor suppressor and ubiquitination-dependent degradation of cytoplasmic beta-catenin. Consistent with this finding, beta-catenin interacted directly with the RA receptor (RAR) in a retinoid-dependent manner, but not with the retinoid X receptor (RXR), and RAR competed with TCF for beta-catenin binding. The activity of RA on RAR-responsive promoters was also potentiated by beta-catenin. The data suggest that direct regulation of beta-catenin-LEF/TCF signaling is one mechanism whereby RA influences development, cell differentiation and cancer.

MeSH terms

  • Caco-2 Cells
  • Cell Line
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Lymphoid Enhancer-Binding Factor 1
  • Mutation
  • Natural Cytotoxicity Triggering Receptor 1
  • Receptors, Immunologic / metabolism
  • Receptors, Retinoic Acid / metabolism
  • Retinoid X Receptors
  • Signal Transduction* / drug effects
  • Trans-Activators*
  • Transcription Factors / metabolism*
  • Tretinoin / pharmacology*
  • Ubiquitins / metabolism
  • beta Catenin


  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Lymphoid Enhancer-Binding Factor 1
  • NCR1 protein, human
  • Natural Cytotoxicity Triggering Receptor 1
  • Receptors, Immunologic
  • Receptors, Retinoic Acid
  • Retinoid X Receptors
  • Trans-Activators
  • Transcription Factors
  • Ubiquitins
  • beta Catenin
  • Tretinoin