To determine the role of β-catenin in cytotoxic effect of CYD-6-17, we established wild-type (WT) or constitutive active (CA) β-catenin-expressing cells, and found that both WT and CA β-catenin could decrease the expression of p21 and p27 and increase the expression of cyclin E and cyclin D1 (Figure 3d), however, under the treatment of CYD-6-17, WT β-catenin failed to rescue CYD-6-17-elicited RCC growth inhibition, CA β-catenin was able to antagonize the inhibitory effect of CYD-6-17 (Figure 3d and Supplementary Figure 4B). Here, CCNE1 is linked to renal cell carcinoma.