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, Irving C. Allen

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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-ΛB 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.

Original languageEnglish (US)
Pages (from-to)33096-33110
Number of pages15
JournalOncotarget
Volume7
Issue number22
DOIs
StatePublished - May 31 2016
Externally publishedYes

Keywords

  • Cancer
  • Inflammation
  • NLR
  • Nod-like receptor
  • Urethane

ASJC Scopus subject areas

  • Oncology

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