Research Papers:

NLRX1 suppresses tumorigenesis and attenuates histiocytic sarcoma through the negative regulation of NF-λB signaling

Sheryl Coutermarsh-Ott _, Alysha Simmons, Vittoria Capria, Tanya LeRoith, Justin E. Wilson, Bettina Heid, Casandra W. Philipson, Qizhi Qin, Raquel Hontecillas-Magarzo, Josep Bassaganya-Riera, Jenny P-Y Ting, Nikolaos Dervisis and Irving C. Allen

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Oncotarget. 2016; 7:33096-33110. https://doi.org/10.18632/oncotarget.8861

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Sheryl Coutermarsh-Ott1, Alysha Simmons1, Vittoria Capria1, Tanya LeRoith1, Justin E. Wilson2, Bettina Heid1, Casandra W. Philipson3, Qizhi Qin1, Raquel Hontecillas-Magarzo3, Josep Bassaganya-Riera3, Jenny P-Y Ting2, Nikolaos Dervisis4, Irving C. Allen1

1Department of Biological Sciences and Pathobiology, Virginia Tech, VA-MD Regional College of Veterinary Medicine, Blacksburg, VA, USA

2Department of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

3Virginia Tech, Virginia Bioinformatics Institute, Nutritional Immunology and Molecular Medicine Laboratory, Blacksburg, VA, USA

4Department of Small Animal Clinical Sciences, Virginia Tech, VA-MD Regional College of Veterinary Medicine, Blacksburg, VA, USA

Correspondence to:

Irving C. Allen, e-mail: [email protected]

Keywords: NLR, Nod-like receptor, urethane, cancer, inflammation

Received: September 09, 2015     Accepted: March 28, 2016     Published: April 20, 2016


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.

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