Cell-Cell Adhesion and Breast Cancer.
Annual rept. 15 Dec 96-14 Dec 97,
GEORGETOWN UNIV WASHINGTON DC
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Our results show that a mesenchymal cadherin, cadherin 11, is expressed in invasive breast cancer cells. The general model that loss of E-cadherin expression or function leads to the invasive, metastatic phenotype may not be the whole picture. Cadherin 11 may be required for cells to acquire a migratory invasive phenotype and may also promote the metastasis of cancer cells to bone where cadherin 11 expressing osteoblasts are present. Other results show that levels of the signaling, oncogenic pool of Beta-catenin in the cytoplasm is regulated by ubiquitination and proteosomal degradation and that mutation of a particular serine S37 inhibits this process. We also show that the tumor suppressor gene APC normally targets beta-catenin for degradation. Our results also show that in addition to its epithelial-differentiation properties, retinoic acid can inhibit the signaling activity of cytoplasmic Beta-cateninLEF. This single result has very important implications in the area of cancer therapeutics. If the anti-cancer effects of retinoic acid are mediated in part by inhibition of Beta-cateninLEF signaling this could lead to the development of agents which specifically inhibit this pathway in cancers which are resistant to the effects of retinoids
- Medicine and Medical Research