Three-dimensional (3D) cultures of MDCK cells have been successfully used as a model to examine abnormal cell growth and polarity, both of which are features of tumorigenic cells.5, 17 Activating mutations or overexpression of HIF2α, Enhancer of zeste homolog 2, β-catenin, K-Ras and H-Ras are particularly frequent in solid tumors.18, 19, 20, 21, 22 Overexpression of β-catenin4A, H-RasV12 or K-RasV12 all led to severely compromised cyst formation resulting in cell clusters with poorly polarized outer epithelial layer surrounding a mass of non-polarized cells (Figures 1a and b). Here, EPAS1 is linked to cyst.