Vitamin A derivatives (retinoids) are potent regulators of embryogenesis, cell proliferation, epithelial cell differentiation and carcinogenesis and 2 over black square]; [1 and 2 over black square]]. In breast cancer cells, the effects of retinoids are associated with changes in the cadherin-beta-catenin adhesion and signaling system  . beta-catenin is a component of the Wnt signaling pathway, which regulates several developmental pathways . Increases in cytoplasmic beta-catenin and beta-catenin signaling are also associated with numerous cancers, and are particularly important in colon cancer . 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   . 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.
Easwaran, V., Pishvaian, M., Salimuddin, & Byers, S. (1999). Cross-regulation of β-catenin–LEF/TCF and retinoid signaling pathways. Current Biology, 9(23), 1415–1419. https://doi.org/10.1016/s0960-9822(00)80088-3