CCNE1 and cancer: Heterogeneity of tumor cells and a biological mechanism involved in this process may be due to Jab1/Csn5, which positively regulates cell proliferation by inactivating p27, cyclin E, Smad 4/7, and p53 or by stabilizing hypoxia inducible factor (HIF-1α), which has been identified as a poor prognostic factor in several cancer types (31).