Lifeguard inhibition of Fas-mediated apoptosis: A possible mechanism for explaining the cisplatin resistance of triple-negative breast cancer cells

Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie
Daniel RadinDonna Leonardi

Abstract

Triple-negative breast cancer does not express estrogen receptor-α, progesterone or the HER2 receptor making hormone or antibody therapy ineffective. Cisplatin may initiate p73-dependent apoptosis in p53 mutant cell lines through Fas trimerization and Caspase-8 activation and Bax up regulation and subsequent Caspase-9 activation. The triple-negative breast cancer, MDA-MB-231, overexpresses the protein Lifeguard, which inhibits Fas-mediated apoptosis by inhibiting Caspase-8 activation after Fas trimerization. The relationship between Fas, Lifeguard and cisplatin is investigated by down regulating Lifeguard via shRNA. Results demonstrate that cisplatin's efficacy increases when Lifeguard is down regulated. Lifeguard Knockdown MDA-MB-231 continue to decrease in cell viability from 24 to 48h after cisplatin treatment while no additional decrease in viability is observed in the Wild-Type MDA over the same period. Higher Caspase-8 activity in the Lifeguard knockdown MDA after cisplatin administration could explain the significant decrease in cell viability from 24 to 48h. This cell type is also more sensitive to Fas ligand-mediated reductions in cell viability, confirming Lifeguard's anti-apoptotic function through the Fas receptor. ...Continue Reading

References

Dec 8, 1998·The Journal of Experimental Medicine·M MüllerP H Krammer
Mar 13, 1999·The Journal of Biological Chemistry·O MicheauM T Dimanche-Boitrel
Oct 27, 1999·Proceedings of the National Academy of Sciences of the United States of America·N V SomiaI M Verma
Dec 18, 2002·Cytokine & Growth Factor Reviews·Harald WajantPeter Scheurich
Jul 22, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Christoph P BeierJörg B Schulz
Aug 9, 2007·European Spine Journal : Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society·Jong-Beom ParkK Daniel Riew
Sep 29, 2009·Apoptosis : an International Journal on Programmed Cell Death·Lan HuGabriel Goldberger
Dec 17, 2009·Proceedings of the National Academy of Sciences of the United States of America·Saskia M BrachmannSauveur-Michel Maira
Mar 26, 2010·Apoptosis : an International Journal on Programmed Cell Death·Vesna BucanKerstin Reimers
Oct 4, 2012·Annals of Oncology : Official Journal of the European Society for Medical Oncology·P Boyle

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Citations

Apr 17, 2016·European Journal of Pharmacology·Daniel P Radin, Parth Patel
Jul 15, 2017·Expert Review of Anticancer Therapy·Aayushi JainNilesh Kumar Sharma
Jan 25, 2019·Oncology Letters·Lingbin MengYing Xin
May 5, 2017·Open Biology·Guia CarraraGeoffrey L Smith
Apr 4, 2019·Journal of the American Chemical Society·Đenana MiodragovićThomas V O'Halloran

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