Tumor suppressor IRF-1 mediates retinoid and interferon anticancer signaling to death ligand TRAIL

The EMBO Journal
Nicole ClarkeHinrich Gronemeyer

Abstract

Retinoids and interferons are signaling molecules with pronounced anticancer activity. We show that in both acute promyelocytic leukemia and breast cancer cells the retinoic acid (RA) and interferon signaling pathways converge on the promoter of the tumoricidal death ligand TRAIL. Promoter mapping, chromatin immunoprecipitation and RNA interference reveal that retinoid-induced interferon regulatory factor-1 (IRF-1), a tumor suppressor, is critically required for TRAIL induction by both RA and IFNgamma. Exposure of breast cancer cells to both antitumor agents results in enhanced TRAIL promoter occupancy by IRF-1 and coactivator recruitment, leading to strong histone acetylation and synergistic induction of TRAIL expression. In coculture experiments, pre-exposure of breast cancer cells to RA and IFNgamma induced a dramatic TRAIL-dependent apoptosis in heterologous cancer cells in a paracrine mode of action, while normal cells were not affected. Our results identify a novel TRAIL-mediated tumor suppressor activity of IRF-1 and suggest a mechanistic basis for the synergistic antitumor activities of certain retinoids and interferons. These data argue for combination therapies that activate the TRAIL pathway to eradicate tumor cells.

References

Jan 1, 1988·Cold Spring Harbor Symposia on Quantitative Biology·D LevyJ E Darnell
Aug 29, 1996·Nature·J Y ChenH Gronemeyer
Feb 7, 1997·International Journal of Cancer. Journal International Du Cancer·S M LippmanU Schleuniger
Jan 1, 1997·Annual Review of Immunology·U BoehmJ C Howard
Nov 5, 1997·Nature Genetics·G S WuW S el-Deiry
Apr 21, 1999·Current Opinion in Cell Biology·A Ashkenazi, V M Dixit
Aug 10, 1999·Seminars in Cell & Developmental Biology·S Minucci, P G Pelicci
Feb 1, 2000·International Journal of Cancer. Journal International Du Cancer·S J UmJ S Park
Apr 5, 2000·The Journal of Biological Chemistry·P GoyetteD Lohnes
Aug 11, 2000·Seminars in Cancer Biology·N Tanaka, T Taniguchi
Oct 12, 2000·Biochemical and Biophysical Research Communications·Q WangB M Evers
Nov 30, 2000·Biochemical and Biophysical Research Communications·B Gong, A Almasan
Nov 13, 2001·Oncogene·F PiazzaP P Pandolfi
Feb 14, 2002·Trends in Biochemical Sciences·Jean-Luc BodmerJürg Tschopp
Feb 14, 2002·Critical Reviews in Oncology/hematology·Shi-Yong Sun, Reuben Lotan
Jan 22, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Erika CretneyMark J Smyth
Jan 24, 2002·Nature·Pierre GermainHinrich Gronemeyer
Feb 16, 2002·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Pierre MorinAhmet Civas
Mar 20, 2002·Cytokine & Growth Factor Reviews·Hiroaki IkedaRobert D Schreiber
Mar 20, 2002·Cytokine & Growth Factor Reviews·Filippo BelardelliJohn M Kirkwood
Mar 21, 2002·Nature Reviews. Cancer·L Altucci, H Gronemeyer
Jul 3, 2002·Nature Reviews. Cancer·Michael B Sporn, Nanjoo Suh
Sep 19, 2002·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Maria A OrtizF Javier Piedrafita
Oct 31, 2002·Nature Immunology·Gavin P DunnRobert D Schreiber
Nov 12, 2002·Nature Medicine·Cornelius SchmaltzMarcel R M van den Brink
Jan 18, 2003·Immunity·Mark J SmythHideo Yagita
May 7, 2003·The Journal of Biological Chemistry·Rong-Lin XieAndre J van Wijnen
Jun 6, 2003·Cytokine & Growth Factor Reviews·Alexandru Almasan, Avi Ashkenazi

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Citations

Oct 11, 2005·Apoptosis : an International Journal on Programmed Cell Death·S-Y Sun
Aug 23, 2011·Apoptosis : an International Journal on Programmed Cell Death·Andrea SgorbissaClaudio Brancolini
Mar 25, 2011·Environmental Health and Preventive Medicine·Tatsushi YoshidaToshiyuki Sakai
Jun 21, 2005·The International Journal of Biochemistry & Cell Biology·Lucia AltucciHinrich Gronemeyer
Nov 26, 2013·Chemical Reviews·Rosana ÁlvarezÁngel R de Lera
Nov 3, 2004·Nature Reviews. Drug Discovery·Hinrich GronemeyerVincent Laudet
Oct 2, 2007·Nature Reviews. Drug Discovery·Lucia AltucciHinrich Gronemeyer
Oct 12, 2010·Oncogene·V PavetH Gronemeyer
May 29, 2007·Oncogene·K TakedaM J Smyth
Sep 8, 2010·The Journal of Biological Chemistry·Angeli MöllerKathryn L Ball
Dec 21, 2004·European Journal of Biochemistry·Sarah SanglierAlain Van Dorsselaer
Jul 5, 2005·Journal of Virology·Jessica R KirshnerPeter M Howley
Feb 29, 2008·Annual Review of Immunology·Tomohiko TamuraTadatsugu Taniguchi
Apr 27, 2010·Annual Review of Nutrition·Noa Noy
Aug 15, 2008·Cancer Research·Jing XuGen Sheng Wu
Nov 15, 2013·Virology Journal·Kaitlin J SoyeBrian J Ward
Oct 8, 2005·Proceedings of the National Academy of Sciences of the United States of America·Sabine RottmannKim C Quon
Jan 19, 2013·Cellular and Molecular Life Sciences : CMLS·Nor Saadah M Azahri, Mary M Kavurma
Sep 8, 2010·Expert Opinion on Therapeutic Targets·Junaid Abdulghani, Wafik S El-Deiry
Jun 20, 2012·Leukemia Research·Mariam ThomasSuzanne Kamel-Reid
Oct 27, 2009·Archives of Medical Research·Patricio GariglioJuan Vázquez
Mar 21, 2009·Cancer Letters·Gen Sheng Wu
Apr 17, 2007·The International Journal of Biochemistry & Cell Biology·Susana AlvarezAngel R de Lera
Oct 3, 2009·The EMBO Journal·Christopher M J WilliamsHelen C Hurst
May 14, 2011·The British Journal of Dermatology·A M NelsonD M Thiboutot
Oct 7, 2004·Trends in Molecular Medicine·A M Jiménez-LaraH Gronemeyer

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