NLRX1 suppresses tumorigenesis and attenuates histiocytic sarcoma through the negative regulation of NF-λB signaling
| Autor: | Josep Bassaganya-Riera, Vittoria Capria, Raquel Hontecillas-Magarzo, Justin E. Wilson, Jenny P.-Y. Ting, Bettina Heid, Alysha Simmons, Irving C. Allen, Casandra Philipson, Sheryl Coutermarsh-Ott, Nikolaos Dervisis, Tanya LeRoith, Qizhi Qin |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Carcinogenesis urethane Histiocytic sarcoma medicine.disease_cause NLR Mitochondrial Proteins Pathogenesis Mice 03 medical and health sciences 0302 clinical medicine medicine cancer Animals Humans NLRX1 Protein kinase B Nod-like receptor business.industry NF-kappa B Cancer medicine.disease Molecular medicine 3. Good health Mice Inbred C57BL Disease Models Animal 030104 developmental biology Oncology inflammation 030220 oncology & carcinogenesis Cancer cell Immunology Cancer research Female Histiocytic Sarcoma business Research Paper Signal Transduction |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Sheryl Coutermarsh-Ott 1 , Alysha Simmons 1 , Vittoria Capria 1 , Tanya LeRoith 1 , Justin E. Wilson 2 , Bettina Heid 1 , Casandra W. Philipson 3 , Qizhi Qin 1 , Raquel Hontecillas-Magarzo 3 , Josep Bassaganya-Riera 3 , Jenny P-Y Ting 2 , Nikolaos Dervisis 4 , Irving C. Allen 1 1 Department of Biological Sciences and Pathobiology, Virginia Tech, VA-MD Regional College of Veterinary Medicine, Blacksburg, VA, USA 2 Department of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA 3 Virginia Tech, Virginia Bioinformatics Institute, Nutritional Immunology and Molecular Medicine Laboratory, Blacksburg, VA, USA 4 Department of Small Animal Clinical Sciences, Virginia Tech, VA-MD Regional College of Veterinary Medicine, Blacksburg, VA, USA Correspondence to: Irving C. Allen, e-mail: icallen@vt.edu Keywords: NLR, Nod-like receptor, urethane, cancer, inflammation Received: September 09, 2015 Accepted: March 28, 2016 Published: April 20, 2016 ABSTRACT Histiocytic sarcoma is an uncommon malignancy in both humans and veterinary species. Research exploring the pathogenesis of this disease is scarce; thus, diagnostic and therapeutic options for patients are limited. Recent publications have suggested a role for the NLR, NLRX1, in acting as a tumor suppressor. Based on these prior findings, we hypothesized that NLRX1 would function to inhibit tumorigenesis and thus the development of histiocytic sarcoma. To test this, we utilized Nlrx1 -/- mice and a model of urethane-induced tumorigenesis. Nlrx1 -/- mice exposed to urethane developed splenic histiocytic sarcoma that was associated with significant up-regulation of the NF-κB signaling pathway. Additionally, development of these tumors was also significantly associated with the increased regulation of genes associated with AKT signaling, cell death and autophagy. Together, these data show that NLRX1 suppresses tumorigenesis and reveals new genetic pathways involved in the pathobiology of histiocytic sarcoma. |
| Databáze: | OpenAIRE |
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