p14(ARF) Prevents Proliferation of Aneuploid Cells by Inducing p53-Dependent Apoptosis

Journal of Cellular Physiology
Lorena VenezianoAldo Di Leonardo

Abstract

Weakening the Spindle Assembly Checkpoint by reduced expression of its components induces chromosome instability and aneuploidy that are hallmarks of cancer cells. The tumor suppressor p14(ARF) is overexpressed in response to oncogenic stimuli to stabilize p53 halting cell progression. Previously, we found that lack or reduced expression of p14(ARF) is involved in the maintenance of aneuploid cells in primary human cells, suggesting that it could be part of a pathway controlling their proliferation. To investigate this aspect further, p14(ARF) was ectopically expressed in HCT116 cells after depletion of the Spindle Assembly Checkpoint MAD2 protein that was used as a trigger for aneuploidy. p14(ARF) Re-expression reduced the number of aneuploid cells in MAD2 post-transcriptionally silenced cells. Also aberrant mitoses, frequently displayed in MAD2-depleted cells, were decreased when p14(ARF) was expressed at the same time. In addition, p14(ARF) ectopic expression in MAD2-depleted cells induced apoptosis associated with increased p53 protein levels. Conversely, p14(ARF) ectopic expression did not induce apoptosis in HCT116 p53KO cells. Collectively, our results suggest that the tumor suppressor p14(ARF) may have an important role...Continue Reading

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Citations

Jun 14, 2020·Genes·Therese WilhelmValeria Naim
Sep 29, 2018·Molecular Genetics and Genomics : MGG·Lorena VenezianoAldo Di Leonardo
Nov 30, 2019·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Ioannis A Voutsadakis
Jul 24, 2020·Genes·Danilo CilluffoAldo Di Leonardo
Jul 10, 2020·International Journal of Molecular Sciences·Raffaella MelfiAldo Di Leonardo
Feb 2, 2021·International Journal of Pharmaceutics·Marina MassaroSerena Riela
Jun 5, 2021·Epigenetics & Chromatin·Xena Giada Pappalardo, Viviana Barra

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