J. Clin. Invest. 109: 987–991 (2002). DOI: 10.1172/JCI200215429. repress its promoter. These include snail, E12/E47, and SIP1, which bind to the CDH1 promoter, inhibit E-cad transcription, and induce an epithelial-to-mesenchymal transition (EMT), leading to acquisition of invasiveness (9–12). The transcriptional repressor snail, a zinc finger protein originally identified as a regulator of mesoderm formation in developing Drosophila, was recently shown to be also critical for EMT in mouse development. In human carcinoma and melanoma, the expression of snail correlates with the absence of E-cad expression. Forced expression of snail in cultured epithelial cells represses the CDH1 promoter and induces a program of invasive growth characterized by the loss of AJs and the induction of EMT and tumorigenesis (9, 10). Interestingly, the invasive areas of mouse skin tumors express the highest levels of snail, supporting the view that activation of snail confers invasive properties on cells (9). E12/E47 and SIP1, which also repress the CDH1 promoter, can likewise induce EMT, increase cell motility and invasion, and confer tumorigenicity. Moreover, SIP1 expression is elevated in several E-cad–negative human carcinoma cells (11). Thus, cancer cells employ reversible or irreversible mechanisms to silence the expression of E-cad. These mechanisms may contribute to enhanced cancer cell motility and invasiveness. The transcriptional mechanisms involved in downregulation of E-cad are similar to those characteristic of typical stages during embryonic development, when changes in cell adhesion and motility take place. Since the loss of E-cad expression is a common feature in many types of carcinoma, and since E-cad reintroduction into cancer cells reduces invasion and metastasis, cancer therapies targeting the regulation of E-cad expression may offer powerful means to control the spread of cancer. A recent study demonstrated that E-cad mRNA expression and cellcell adhesion are induced in SW480 human colon cancer cells by vitamin D3 (13). This makes vitamin D3 a potential candidate for treating colon cancer by inhibiting cell growth, similar to its effect on melanoma and soft tissue sarcoma.