Tumor and Stem Cell Biology Numb Regulates Stability and Localization of the Mitotic Kinase PLK1 and Is Required for Transit through Mitosis

Numb functions in progenitor cell fate determination and early development, but it is also expressed in postdevelopmental tissues and cancers where its role is unclear. In this study, we report that a targeted knockdown of Numb expression causes a G2–M arrest and reduced cell growth in human melanoma cells. Coimmunoprecipitation and colocalization studies showed that Numb interacts with the serine/threonine polo-like kinase Plk1 and Numb cycles in a cell-cycle–dependent fashion along with this mitotic regulator. Interestingly, Numb expression was required for Plk1 protein stability and localization to the spindle poles during mitosis. Reduction in Numb expression resulted in mislocalization of Plk1 at both metaphase and anaphase, leading to disorganized g-tubulin recruitment in centrosomes. Together, our findings present a novel function for Numb during symmetric cell division. We suggest that dysregulation of Numb expression results in mislocalized Plk1 and poor centrosomal g-tubulin recruitment, potentially contributing to mitotic errors, aneuploidy, and cancer development. Cancer Res; 72(15); 3864–72. 2012 AACR.