Figure 2. Stage-specific roles for p21^WAF1 in epithelial carcinogenesis. p21^WAF1 is involved in several normal cellular processes, including cell cycle progression, cell differentiation, and senescence. p21^WAF1 also has an inhibitory effect on the initiation/promotion stage(s) of carcinogenesis, thereby reducing the formation of papillomas, but does not affect conversion of these benign tumors to carcinomas. Once a carcinoma is established, however, p21^WAF1 helps maintain it in a well-differentiated state, thus impeding progression to spindle cell carcinomas.