Abstract: An embodiment of the invention provides methods and compositions for immortalizing cells, and in another embodiment for reversing immortalization of cells. Methods for screening for anti-cancer agents by identifying compounds that bind to and inhibit activity of an Ndy protein are also provided. Novel cancer diagnostic and prognostic methods using Ndy1, Ezh2 and miR-101 are shown with samples of tissue or cell lines from cancers of lung, colon, ovary, bladder and transitional cell carcinoma.