Promising roles of mammalian E2Fs in hepatocellular carcinoma

In mammalian cells, E2F family of transcription factors (E2Fs) traditionally modulates assorted cellular functions related to cell cycle progression, proliferation, apoptosis and differentiation. Eight members, E2F1 E2F8 have been recognized of this family so far, and the members of this family are generally divided into activator E2F (E2F1--E2F3a), repressor E2F (E2F3b--E2F5) and inhibitor E2F (E2F6--E2F8) subclasses based on their structur-e and function. Studies have showed that the mammalian E2F family members represent a recent evolutionary adaptation to malignancies besides hepatocellular carcinoma (HCC), and a growing body of evidence has validated that the individual members of the family develop a close relationship with HCC. E2F1 was identified to play overlapping roles in HCC, while E2F2--E2F8 (except E2F6 and E2F7) showed to be tumor-promoter in HCC. However, the mechanism underlying the mammalian E2Fs associated with HCC is still unknown and needs further research. The aim of this review is to sum up the collective knowledge of E2F family and the roles of each member of this family in HCC. Moreover, we will discuss some novel therapeutic target for HCC based on the complicated functions of mammalian E2Fs.