p21/cyclin E pathway modulates anticlastogenic function of Bmi-1 in cancer cells

Wen Deng, Yuan Zhou, Agnes F.Y. Tiwari, Hang Su, Jie Yang, Dandan Zhu, Victoria Ming Yi Lau, Pok Man Hau, Yim Ling Yip, Annie L.M. Cheung, Xin Yuan Guan, George Sai Wah Tsao

    Research output: Contribution to journalArticle

    6 Scopus citations

    Abstract

    Apart from regulating stem cell self-renewal, embryonic development and proliferation, Bmi-1 has been recently reported to be critical in the maintenance of genome integrity. In searching for novel mechanisms underlying the anticlastogenic function of Bmi-1, we observed, for the first time, that Bmi-1 positively regulates p21 expression. We extended the finding that Bmi-1 deficiency induced chromosome breaks in multiple cancer cell models. Interestingly, we further demonstrated that knockdown of cyclin E or ectopic overexpression of p21 rescued Bmi-1 deficiency-induced chromosome breaks. We therefore conclude that p21/cyclin E pathway is crucial in modulating the anticlastogenic function of Bmi-1. As it is well established that the overexpression of cyclin E potently induces genome instability and p21 suppresses the function of cyclin E, the novel and important implication from our findings is that Bmi-1 plays an important role in limiting genomic instability in cylin E-overexpressing cancer cells by positive regulation of p21.

    Original languageEnglish (US)
    Pages (from-to)1361-1370
    Number of pages10
    JournalInternational Journal of Cancer
    Volume136
    Issue number6
    DOIs
    StatePublished - Mar 15 2015

    Keywords

    • Bmi-1
    • Cyclin E
    • Genomic instability
    • Replicative stress
    • p21

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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  • Cite this

    Deng, W., Zhou, Y., Tiwari, A. F. Y., Su, H., Yang, J., Zhu, D., Lau, V. M. Y., Hau, P. M., Yip, Y. L., Cheung, A. L. M., Guan, X. Y., & Tsao, G. S. W. (2015). p21/cyclin E pathway modulates anticlastogenic function of Bmi-1 in cancer cells. International Journal of Cancer, 136(6), 1361-1370. https://doi.org/10.1002/ijc.29114