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Niklas Finnberg, … , Andres J.P. Klein-Szanto, Wafik S. El-Deiry
Published December 13, 2007
Citation Information: J Clin Invest. 2008;118(1):111-123. https://doi.org/10.1172/JCI29900.
Citation Information: J Clin Invest. 2008;118(1):111-123. https://doi.org/10.1172/JCI29900.
Abstract
Preclinical data support the potential of the death-signaling receptors for TRAIL as targets for cancer therapy. However, it is unclear whether these death-signaling receptors suppress the emergence and growth of malignant tumors in vivo. Herein we show that TNF-related apoptosis-inducing ligand receptor (TRAIL-R), the only proapoptotic death-signaling receptor for TRAIL in the mouse, suppresses inflammation and tumorigenesis. Loss of a single TRAIL-R allele on the lymphoma-prone Eμ-myc genetic background significantly reduced median lymphoma-free survival. TRAIL-R–deficient lymphomas developed with equal frequency irrespective of mono- or biallelic loss of TRAIL-R, had increased metastatic potential, and showed apoptotic defects relative to WT littermates. In addition, TRAIL-R–/– mice showed decreased long-term survival following a sublethal dose of ionizing radiation. Histological evaluation of moribund irradiated TRAIL-R–/– animals showed hallmarks of bronchopneumonia as well as tumor formation with increased NF-κB p65 expression. TRAIL-R also suppressed diethylnitrosamine-induced (DEN-induced) hepatocarcinogenesis, as an increased number of large tumors with apoptotic defects developed in the livers of DEN-treated TRAIL-R–/– mice. Thus TRAIL-R may function as an inflammation and tumor suppressor in multiple tissues in vivo.
Authors
Niklas Finnberg, Andres J.P. Klein-Szanto, Wafik S. El-Deiry
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Citation information
Citations to this article (100)
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Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology | 2009 |
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Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) in central nervous system inflammation
O Hoffmann, F Zipp, JR Weber |
Journal of Molecular Medicine | 2009 |
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Following TRAIL’s path in the immune system
C Falschlehner, U Schaefer, H Walczak |
Immunology | 2009 |
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Oncogenic stress sensed by the immune system: role of natural killer cell receptors
DH Raulet, N Guerra |
Nature Reviews Immunology | 2009 |
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Life and death by death receptors
ME Guicciardi, GJ Gores |
The FASEB Journal | 2009 |
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Death Receptor 5 Internalization Is Required for Lysosomal Permeabilization by TRAIL in Malignant Liver Cell Lines
Y Akazawa, JL Mott, SF Bronk, NW Werneburg, A Kahraman, ME Guicciardi, XW Meng, S Kohno, VH Shah, SH Kaufmann, MA McNiven, GJ Gores |
Gastroenterology | 2009 |
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Death receptor signal transducers: nodes of coordination in immune signaling networks
NS Wilson, V Dixit, A Ashkenazi |
Nature Immunology | 2009 |
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Gene polymorphisms, apoptotic capacity and cancer risk.
Imyanitov EN |
Human Genetics | 2009 |
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Combination of isoliquiritigenin and tumor necrosis factor-related apoptosis-inducing ligand induces apoptosis in colon cancer HT29 cells
T Yoshida, M Horinaka, M Takara, M Tsuchihashi, N Mukai, M Wakada, T Sakai |
Environmental Health and Preventive Medicine | 2008 |
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TRAIL receptor-targeted therapeutics: resistance mechanisms and strategies to avoid them
A Thorburn, K Behbakht, H Ford |
Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy | 2008 |
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Cancer stem cells and immunoresistance: clinical implications and solutions
Jordi Codony-Servat, Rafael Rosell |
Translational Lung Cancer Research | |
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Agonists of the TRAIL Death Receptor DR5 Sensitize Intestinal Stem Cells to Chemotherapy-Induced Cell Death and Trigger Gastrointestinal Toxicity
NK Finnberg, P Gokare, A Navaraj, KA Kuhs, G Cerniglia, H Yagita, K Takeda, N Motoyama, WS El-Deiry |
Cancer research | 2015 |
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Metastasis Suppressor Function of Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand-R in Mice: Implications for TRAIL-Based Therapy in Humans?: Figure 1
A Grosse-Wilde, CJ Kemp |
Cancer research | 2008 |
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