Oncolytic targeting of renal cell carcinoma via encephalomyocarditis virus.

EMBO Molecular Medicine
Frederik C RoosMichael Ohh

Abstract

Apoptosis is a fundamental host defence mechanism against invading microbes. Inactivation of NF-kappaB attenuates encephalomyocarditis virus (EMCV) virulence by triggering rapid apoptosis of infected cells, thereby pre-emptively limiting viral replication. Recent evidence has shown that hypoxia-inducible factor (HIF) increases NF-kappaB-mediated anti-apoptotic response in clear-cell renal cell carcinoma (CCRCC) that commonly exhibit hyperactivation of HIF due to the loss of its principal negative regulator, von Hippel-Lindau (VHL) tumour suppressor protein. Here, we show that EMCV challenge induces a strong NF-kappaB-dependent gene expression profile concomitant with a lack of interferon-mediated anti-viral response in VHL-null CCRCC, and that multiple established CCRCC cell lines, as well as early-passage primary CCRCC cultured cells, are acutely susceptible to EMCV replication and virulence. Functional restoration of VHL or molecular suppression of HIF or NF-kappaB dramatically reverses CCRCC cellular susceptibility to EMCV-induced killing. Notably, intratumoural EMCV treatment of CCRCC in a murine xenograft model rapidly regresses tumour growth. These findings provide compelling pre-clinical evidence for the usage of EMCV in...Continue Reading

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References

Nov 1, 1990·The Journal of General Virology·J D WilliamsonM Mackett
Feb 1, 1995·Current Opinion in Genetics & Development·Y Shen, T E Shenk
Jan 1, 1994·Annual Review of Immunology·P A Baeuerle, T Henkel
Nov 1, 1996·Science·D J Van AntwerpI M Verma
Mar 1, 1997·Journal of Virology·J G Teodoro, P E Branton
Feb 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·J BertinJ I Cohen
May 11, 2002·Nature Reviews. Cancer·Michael KarinZhi-Wei Li
Sep 5, 2002·Nature Reviews. Cancer·William G Kaelin
Sep 19, 2002·Biochemical and Biophysical Research Communications·Yoon Ki Kim, Sung Key Jang
Dec 3, 2002·Nature Reviews. Cancer·E Antonio Chiocca
Jan 23, 2003·Proceedings of the National Academy of Sciences of the United States of America·Shinyop KimTak W Mak
Mar 23, 2004·Current Gene Therapy·S M NgoiC G L Lee
Sep 17, 2004·Genes & Development·Matthew S Hayden, Sankar Ghosh
Apr 16, 2005·Neuro-oncology·Balveen KaurErwin G Van Meir
May 10, 2005·Diagnostic Cytopathology·Maria Sironi, Gianni Tunesi
Jun 23, 2005·Drug Discovery Today·Kara L Norman, Patrick W K Lee
Aug 19, 2005·Molecular and Cellular Biology·Jiabin An, Matthew B Rettig
Nov 22, 2005·Oncogene·Manish Aghi, Robert L Martuza
Dec 13, 2005·The New England Journal of Medicine·Herbert T Cohen, Francis J McGovern
Apr 28, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Scott A LaurieRobert M Lorence
Sep 19, 2006·The Journal of Biological Chemistry·Ian R WatsonMeredith S Irwin
Oct 25, 2006·Molecular and Cellular Biology·Andrew J EvansMichael Ohh
Nov 29, 2007·Current Opinion in Oncology·Andrew M Roberts, Michael Ohh
Jan 30, 2009·Antiviral Research·Dale L Barnard
Jul 3, 2009·Current Opinion in Urology·M Pilar LagunaJean J M C H de la Rosette

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Citations

Apr 21, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Elizabeth M HadacStephen J Russell
Jul 12, 2012·Nature Biotechnology·Stephen J RussellJohn C Bell
Apr 11, 2013·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Siddharth Balachandran, Gregory P Adams
Mar 20, 2013·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Wei-Choong Ch'ngNorazizah Shafee
Oct 12, 2013·PloS One·Suraj PeriSiddharth Balachandran
May 9, 2012·Expert Opinion on Biological Therapy·Keith A Lawson, Don G Morris
May 12, 2011·Reviews in Medical Virology·Danijela Koppers-Lalic, Rob C Hoeben
Jun 23, 2012·Virulence·Margot Carocci, Labib Bakkali-Kassimi
Dec 3, 2016·The Journal of General Virology·Noraini Abd-AzizNorazizah Shafee
May 19, 2019·Cancers·Cormac McCarthyMihnea Bostina
Nov 11, 2018·Cancers·Justyna Struzik, Lidia Szulc-Dąbrowska
May 10, 2013·Molecular Cancer Therapeutics·Roshan J ThapaSiddharth Balachandran

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Datasets Mentioned

BETA
E-MTAB-294

Methods Mentioned

BETA
xenografts
nuclear translocation
PCR
light microscopy
electron microscopy
pull-down
xenograft
biopsy
transgenic
flow cytometry

Software Mentioned

Affymetrix
GraphPad Prism
Microarray Analysis Suite
ImageJ
GraphPad
ArrayExpress
Primer Express

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis