Abstract
The transcription factor E2F1 exhibits dual properties, acting as a tumor suppressor and oncogene. Cellular stress such as DNA damage or mitogenic signaling leads to the activation of E2F1 as a mediator of apoptosis in the context of a conserved cellular anti-tumorigenic safeguard mechanism. However in highly aggressive chemoresistant tumors like malignant melanoma and prostate/bladder cancer it switches off this role and acts as promoter of cancer progression. Possible reasons for E2F1 mediated aggressiveness are defects in cell death pathways caused by epigenetic inactivation of important tumor suppressor genes, which often occur in late stage cancer and contribute to chemoresistance. Nevertheless exact mechanisms underlying E2Fs role in invasiveness and metastasis are largely unknown. Different reports hint towards the existence of feedback loops between E2F1 and microRNAs (miRNAs or miRs). MiRs are activated by E2F1 and either the transcription factor itself or cellular genes necessary for the growth regulating function of E2F1 are inhibited by different miRNAs. This mutual regulation possibly influences the balance between E2F1s proapoptotic versus prosurvival function. In the following we will summarize some miRNA-E2F1-interactions contributing to a complex regulatory network.
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Acknowledgements
Work related to this review was supported by grants from the Deutsche Krebshilfe and FORUN program of Rostock University Medical Faculty. S. Knoll receives a fellowship of the Landesgraduiertenfƶrderung des Landes Mecklenburg-Vorpommern.
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Knoll, S., Emmrich, S., PĆ¼tzer, B.M. (2013). The E2F1-miRNA Cancer Progression Network. In: Schmitz, U., Wolkenhauer, O., Vera, J. (eds) MicroRNA Cancer Regulation. Advances in Experimental Medicine and Biology, vol 774. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5590-1_8
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