Cellular senescence induced by aberrant MAD2 levels impacts on paclitaxel responsiveness in vitro.

British Journal of Cancer
M PrencipeA McCann

Abstract

The mitotic arrest deficiency protein 2 (MAD2) is a key component of the mitotic spindle assembly checkpoint, monitoring accurate chromosomal alignment at the metaphase plate before mitosis. MAD2 also has a function in cellular senescence and in a cell's response to microtubule inhibitory (MI) chemotherapy exemplified by paclitaxel. Using an siRNA approach, the impact of MAD2 down-regulation on cellular senescence and paclitaxel responsiveness was investigated. The endpoints of senescence, cell viability, migration, cytokine expression, cell cycle analysis and anaphase bridge scoring were carried out using standard approaches. We show that MAD2 down-regulation induces premature senescence in the MCF7 breast epithelial cancer cell line. These MAD2-depleted (MAD2) cells are also significantly replicative incompetent but retain viability. Moreover, they show significantly higher levels of anaphase bridges and polyploidy compared to controls. In addition, these cells secrete higher levels of IL-6 and IL-8 representing key components of the senescence-associated secretory phenotype (SASP) with the ability to impact on neighbouring cells. In support of this, MAD2 cells show enhanced migratory ability. At 72 h after paclitaxel, MAD2 c...Continue Reading

References

May 31, 1990·Nature·C B HarleyC W Greider
Oct 11, 1996·Science·Y Li, R Benezra
Apr 10, 1997·Nature·C LengauerB Vogelstein
Jan 1, 1999·Nature·C LengauerB Vogelstein
Apr 13, 2000·Proceedings of the National Academy of Sciences of the United States of America·B D ChangI B Roninson
Nov 7, 2000·Genes, Chromosomes & Cancer·M J PercyE M Petty
Dec 26, 2001·Proceedings of the National Academy of Sciences of the United States of America·Bey-Dih ChangIgor B Roninson
Aug 7, 2002·The American Journal of Pathology·Dae-Sung YoonEdward Gabrielson
Jul 25, 2003·Cancer Biology & Therapy·William Saunders
Jul 25, 2003·Cancer Biology & Therapy·Louis K SussmanLaura E Benjamin
Aug 13, 2003·The EMBO Journal·Christian M BeauséjourJudith Campisi
Mar 1, 1965·Experimental Cell Research·L HAYFLICK
Jan 7, 2004·Nature Reviews. Molecular Cell Biology·Zuzana Storchova, David Pellman
Apr 3, 2004·Cancer Research·Tamotsu SudoNaoto T Ueno
Apr 13, 2004·Oncogene·Jerry W Shay, Igor B Roninson
Dec 8, 2004·Experimental Gerontology·Barbara HampelPidder Jansen-Dürr
Aug 5, 2005·Nature·Manuel ColladoManuel Serrano
Apr 22, 2006·Cell Cycle·Charles SwantonJulian Downward
Apr 5, 2007·Nature Protocols·Nicolaas A P FrankenChris van Bree
May 1, 2007·Biochimica Et Biophysica Acta·Maggie K-L FungXianghong Wang
Jan 15, 2008·Oncogene·S Courtois-CoxK Cichowski
Jan 10, 2009·Nature Reviews. Cancer·Thomas Kuilman, Daniel S Peeper
Feb 17, 2009·EMBO Reports·Andrew R J Young, Masashi Narita

❮ Previous
Next ❯

Citations

Jul 26, 2015·Cell Cycle·Ian J RestallIan A J Lorimer
Oct 11, 2011·Molecular Cancer·Amanda J O'NeillR William G Watson
Nov 26, 2014·Proceedings of the National Academy of Sciences of the United States of America·Steven Setiawan ThengCaroline G Lee
Sep 6, 2017·Cell Cycle·Jeeyeon M Cha, David M Aronoff
Jul 8, 2017·Endocrine-related Cancer·Bing Cheng, Karen Crasta
May 19, 2011·Nature Reviews. Clinical Oncology·Katsumi Kitagawa
Jun 5, 2019·International Journal of Molecular Sciences·Yu-Hsuan LeeRong-Jane Chen
Oct 18, 2015·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·A M MonganJ O'Sullivan
Aug 8, 2015·The Prostate·Maria PrencipeR William Watson
Jul 15, 2017·Cellular and Molecular Life Sciences : CMLS·Corinne AbbadieAlbin Pourtier
Feb 29, 2020·Indian Journal of Pathology & Microbiology·Abhilash DeoPritha Ray
Jul 26, 2017·Cancer Chemotherapy and Pharmacology·Xingjuan Shi, Xiaoou Sun
Jan 8, 2021·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·Sinjini SarkarVilas D Nasare
Dec 4, 2020·European Journal of Pharmacology·Alicja UrbaniakTimothy C Chambers

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Methods Mentioned

BETA
chromosomal aberration
transfection
electrophoresis
fluorescence-activated cell sorting
FACS
ELISA

Software Mentioned

Scion
Summit

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