Upregulation of E2F8 promotes cell proliferation and tumorigenicity in breast cancer by modulating G1/S phase transition

Liping Ye, Ling Guo, Zhenyu He, Xi Wang, Chuyong Lin, Xin Zhang, Shu Wu, Yong Bao, Qi Yang, Libing Song, Huanxin Lin

    Research output: Contribution to journalArticle

    25 Scopus citations

    Abstract

    E2F transcription factors are involved in cell cycle regulation and synthesis of DNA in mammalian cells, and simultaneously play important roles in the development and progression of cancer when dysregulated. E2F8, a novel identified E2F family member, was found to be associated with the progression of several human cancers; however, the biological role and clinical significance of E2F8 in breast cancer remain to be further elucidated. Herein, we report that E2F8 is robustly elevated in breast cancer cell lines and clinical breast cancer tissue samples, respectively. The high expression level of E2F8 significantly correlates with clinical progression (P = 0.001), poor patient survival (P < 0.001) and a high Ki67 staining index (P = 0.008) in 187 human breast cancer specimens. Furthermore, we find that overexpressing E2F8 promotes, whereas silencing E2F8 suppresses, the proliferation and tumorigenicity of breast cancer cells both in vitro and in vivo. We further demonstrate that E2F8 transcriptionally upregulates CCNE1 and CCNE2 via directly interacting with their respective gene promoter, which accelerates the transition of G1 to S phase of breast cancer cells. Taken together, these findings uncover a novel biologic role and regulatory mechanism of E2F8 responsible for the progression of breast cancer, indicating E2F8 may represent a novel prognostic biomarker and therapeutic target against breast cancer.

    Original languageEnglish (US)
    Pages (from-to)23757-23771
    Number of pages15
    JournalOncotarget
    Volume7
    Issue number17
    DOIs
    StatePublished - Apr 26 2016

    Keywords

    • Breast cancer
    • Cell cycle
    • E2F8
    • Proliferation
    • Tumorigenicity

    ASJC Scopus subject areas

    • Oncology

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  • Cite this

    Ye, L., Guo, L., He, Z., Wang, X., Lin, C., Zhang, X., Wu, S., Bao, Y., Yang, Q., Song, L., & Lin, H. (2016). Upregulation of E2F8 promotes cell proliferation and tumorigenicity in breast cancer by modulating G1/S phase transition. Oncotarget, 7(17), 23757-23771. https://doi.org/10.18632/oncotarget.8121