Cancer Biology and Pharmacology, Genome Institute of Singapore, A*STAR (Agency for Science, Technology and Research), Biopolis, Singapore.
Curr Mol Pharmacol. 2009 Jun;2(2):149-60. doi: 10.2174/1874467210902020149.
The development of cancer depends on the delicate balance between cell proliferation and programmed cell death. p16(INK4a) -cyclinD/cdk4-pRb-E2F1 is a critical pathway regulating cell proliferation in which E2F1 is an important downstream effector. Deregulated E2F1 activity due to the aberrance of the upstream components in this pathway, such as inactivation of Rb or p16, or amplification of cyclinD or cdk4, confers growth advantage to cancer cells and has thus become a hallmark of human tumors. In addition to cell proliferation control, compelling evidence indicates that E2F1 can also induce apoptosis under various cellular contexts regardless of p53 status. Given the frequent inactivation of tumor suppressor pRb and p53 in human cancers, E2F1- induced apoptosis might serve as an additional tumor surveillance mechanism to protect the organism from tumor development. E2F1-mediated apoptosis pathway is therefore emerging as a promising target for therapeutic intervention. Here, we review the recent advances in the understanding of E2F1-mediated apoptosis in cancer cells and discuss how these discoveries may expand our view of E2F1 signaling network and contribute to the development of novel therapeutic strategy.
癌症的发展取决于细胞增殖和程序性细胞死亡之间的微妙平衡。p16(INK4a)-cyclinD/cdk4-pRb-E2F1 是调节细胞增殖的关键途径，其中 E2F1 是一个重要的下游效应因子。由于该途径上游成分（如 Rb 或 p16 的失活、cyclinD 或 cdk4 的扩增）的失常，导致 E2F1 活性失调，赋予癌细胞生长优势，因此已成为人类肿瘤的标志。除了控制细胞增殖外，大量证据表明，E2F1 可以在各种细胞环境下诱导细胞凋亡，而不依赖于 p53 状态。鉴于肿瘤抑制因子 pRb 和 p53 在人类癌症中经常失活，E2F1 诱导的细胞凋亡可能作为一种额外的肿瘤监测机制，以保护机体免受肿瘤的发生。因此，E2F1 介导的细胞凋亡途径正成为治疗干预的一个有前途的靶点。在这里，我们综述了近年来对 E2F1 介导的癌细胞凋亡的理解方面的进展，并讨论了这些发现如何扩展我们对 E2F1 信号网络的认识，并有助于开发新的治疗策略。
