The tumor suppressor p14ARF hampers proliferation of aneuploid cells induced by CENP-E partial depletion

The Spindle Assembly Checkpoint (SAC) is a cellular surveillance mechanism that ensures faithfully segregation of chromosomes. Reduced expression of some of its components weakens the SAC and induces chromosome instability and aneuploidy, both hallmarks of tumor cells. Centromere Protein-E (CENP-E) is a crucial component of the SAC and facilitates kinetochore microtubule attachment required to achieve and maintain chromosome alignment. To investigate the possible role of p14ARF on aneuploid cells proliferation we induced aneuploidy in primary human fibroblasts (IMR90) and in near diploid tumor cells (HCT116) by partial depletion of CENP-E obtained by RNA interference. Our results show that in contrast to IMR90 aneuploid cell number that was drastically reduced tending toward wild type condition, HCT116 aneuploid cells were slightly decreased at late time points. This euploidy restoration was accompanied by increased p14ARF expression in IMR90 cells and followed ectopic p14ARF re-expression in p14ARF-null HCT116 cells. Collectively, our results strongly suggest that hampering proliferation of aneuploid cells is an additional role of the p14ARF tumor suppressor.