Voltage dependent anion channel-1 regulates death receptor mediated apoptosis by enabling cleavage of caspase-8.

BMC Cancer
Alex D ChackoDean A Fennell

Abstract

Activation of the extrinsic apoptosis pathway by tumour necrosis factor related apoptosis inducing ligand (TRAIL) is a novel therapeutic strategy for treating cancer that is currently under clinical evaluation. Identification of molecular biomarkers of resistance is likely to play an important role in predicting clinical anti tumour activity. The involvement of the mitochondrial type 1 voltage dependent anion channel (VDAC1) in regulating apoptosis has been highly debated. To date, a functional role in regulating the extrinsic apoptosis pathway has not been formally excluded. We carried out stable and transient RNAi knockdowns of VDAC1 in non-small cell lung cancer cells, and stimulated the extrinsic apoptotic pathway principally by incubating cells with the death ligand TRAIL. We used in-vitro apoptotic and cell viability assays, as well as western blot for markers of apoptosis, to demonstrate that TRAIL-induced toxicity is VDAC1 dependant. Confocal microscopy and mitochondrial fractionation were used to determine the importance of mitochondria for caspase-8 activation. Here we show that either stable or transient knockdown of VDAC1 is sufficient to antagonize TRAIL mediated apoptosis in non-small cell lung cancer (NSCLC) cell...Continue Reading

References

May 31, 1996·The Journal of Biological Chemistry·R M PittiA Ashkenazi
Aug 28, 1998·Science·A Ashkenazi, V M Dixit
Oct 9, 1998·The Journal of Biological Chemistry·H R StennickeG S Salvesen
Dec 26, 2001·The Journal of Biological Chemistry·John G PastorinoJan B Hoek
Mar 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·David G BreckenridgeGordon C Shore
Jun 1, 2002·Science·Harald Wajant
Jul 26, 2003·Science·Emily H Y ChengStanley J Korsmeyer
Sep 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Elizabeth A JonasLeonard K Kaczmarek
Oct 12, 2004·The International Journal of Biochemistry & Cell Biology·Alfons LawenVito De Pinto
Apr 10, 2007·Nature Cell Biology·Christopher P BainesJeffery D Molkentin
Apr 3, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shaopeng YuanYongzhang Luo
Jul 22, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Avi AshkenaziS Gail Eckhardt
Nov 8, 2008·Nature Reviews. Drug Discovery·Avi Ashkenazi
Nov 13, 2008·The Journal of Cell Biology·Francois GonzalvezEyal Gottlieb
May 23, 2009·Journal of Cell Science·Salah Abu-HamadVarda Shoshan-Barmatz

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Citations

Jun 25, 2013·Biochemical and Biophysical Research Communications·Adrianna L HensonSteven R Ellis
Dec 3, 2014·Biochimica Et Biophysica Acta·Debanjan TewariAmal Kanti Bera
Aug 30, 2012·The Journal of Physiology·Harpreet SinghLigia Toro
Jul 26, 2011·Free Radical Biology & Medicine·Tanea T Reed
Sep 18, 2014·CNS Neuroscience & Therapeutics·Ruo-Yang ShiJi-Ming Kong
May 22, 2013·Evidence-based Complementary and Alternative Medicine : ECAM·Yin-Quan TangShamala Devi Sekaran
Mar 8, 2018·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Paula M MiottoGraham P Holloway
Aug 9, 2015·The Journal of Biological Chemistry·Li HuangQuan Chen
Aug 22, 2017·Frontiers in Oncology·Varda Shoshan-BarmatzTasleem Arif

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Methods Mentioned

BETA
Flow cytometry
Confocal microscopy
transfection
electrophoresis
Assay

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