| Autor: |
McFadden, Rita-Marie T., Li, Zengshan, Brickey, W. June, Lund, Pauline Kay, Koblansky, A. Alicia, Jobin, Christian, Liu, Rongrong, Ding, Shengli, Montgomery, Stephanie A., Hu, Peizhen, Wilson, Justin E., Ting, Jenny P.-Y., Mühlbauer, Marcus, Truax, Agnieszka D. |
| Jazyk: |
angličtina |
| Předmět: |
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| Popis: |
NOD-like receptor (NLR) proteins are intracellular innate immune sensors/receptors that regulate immunity. This work shows that NLRX1 serves as a tumor suppressor in colitis-associated cancer (CAC) and sporadic colon cancer by keeping key tumor promoting pathways in check. Nlrx1(-/-) mice were highly susceptible to CAC, showing increases in key cancer-promoting pathways including nuclear factor κB (NF-κB), mitogen-activated protein kinase (MAPK), signal transducer and activator of transcription 3 (STAT3), and interleukin 6 (IL-6). The tumor-suppressive function of NLRX1 originated primarily from the non-hematopoietic compartment. This prompted an analysis of NLRX1 function in the Apc(min/+) genetic model of sporadic gastrointestinal cancer. NLRX1 attenuated Apc(min/+) colon tumorigenesis, cellular proliferation, NF-κB, MAPK, STAT3 activation, and IL-6 levels. Application of anti-interleukin 6 receptor (IL6R) antibody therapy reduced tumor burden, increased survival, and reduced STAT3 activation in Nlrx1(-/-)Apc(min/+) mice. As an important clinical correlate, human colon cancer samples expressed lower levels of NLRX1 than healthy controls in multiple patient cohorts. These data implicate anti-IL6R as a potential personalized therapy for colon cancers with reduced NLRX1. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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