A sustained small increase in NOD1 expression promotes ligand-independent oncogenic activity
| Autor: | Iain D. C. Fraser, Carolyn Hutcheon, Nicolas W. Lounsbury, Naeha Subramanian, Ronald N. Germain, Bhaskar Dutta, Ram Savan, Clifford Rostomily, Leah M. Rommereim, Ajay Suresh Akhade |
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| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Poor prognosis Oncogene Chemistry Complex disease Inflammation Cell biology body regions Persistent inflammation 03 medical and health sciences 0302 clinical medicine Transcription (biology) 030220 oncology & carcinogenesis NOD1 Gene expression medicine medicine.symptom 030304 developmental biology |
| DOI: | 10.1101/518886 |
| Popis: | Small genetically-determined differences in transcription (eQTLs) are implicated in complex disease but the mechanisms by which small changes in gene expression impact complex disease are unknown. Here we show that a persistent small increase in expression of the innate sensor NOD1 precipitates large cancer-promoting changes in cell state. A ~1.2-1.4 fold increase in NOD1 protein concentration by loss of miR-15b/16 regulation sensitizes cells to ligand-induced inflammation, with an additional slight increase leading to ligand-independent NOD1 activation that is linked to poor prognosis in gastric cancer. Our data show that tight expression regulation of NOD1 prevents this sensor from exceeding a physiological switching checkpoint that promotes persistent inflammation and oncogene expression and reveal the impact of a single small quantitative change in cell state on cancer.One Sentence SummaryA small change in NOD1 expression has a large cancer-promoting impact on cell state. |
| Databáze: | OpenAIRE |
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