E2F8, a member of the E2F family, is a multifaceted transcription factor. It has a duplicated DNA-binding domain, distinguishing it from E2F1-6, and controls gene expression in a dimerization-partner-independent manner. E2F8 is crucial for angiogenesis, lymphangiogenesis, and embryonic development, and is involved in pathways like cell-cycle regulation, such as the G1-to-S-phase transition [1].

E2F8 shows diverse roles in different diseases. In hepatocellular carcinoma (HCC), it promotes cancer occurrence and development via the E2F1/Cyclin D1 signaling pathway or by transcriptionally suppressing CDK1 [1]. In cervical and ovarian cancers, E2F8 is associated with cancer progression, regulating cell proliferation, invasion, and epithelial-mesenchymal transition (EMT) [2,5]. In breast cancer, E2F8 contributes to homologous recombination repair and chemoresistance through the E2F8-CENPL pathway [4]. In contrast, in the human placenta, it may suppress the invasiveness of extravillous trophoblasts, different from its role in the murine placenta [3].

In conclusion, E2F8 is essential for multiple biological processes and embryonic development. Its dysregulation is closely associated with various cancers, making it a potential therapeutic target. Research on E2F8, especially through gene-knockout or conditional-knockout models in mice, helps in understanding its role in disease mechanisms, offering insights for developing new treatment strategies for cancer and other related diseases.