%0 Journal Article %A Leah M. Rommereim %A Ajay Suresh Akhade %A Bhaskar Dutta %A Carolyn Hutcheon %A Nicolas W. Lounsbury %A Clifford C. Rostomily %A Ram Savan %A Iain D. C. Fraser %A Ronald N. Germain %A Naeha Subramanian %T A sustained small increase in NOD1 expression promotes ligand-independent oncogenic activity %D 2019 %R 10.1101/518886 %J bioRxiv %P 518886 %X 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 Summary A small change in NOD1 expression has a large cancer-promoting impact on cell state. %U https://www.biorxiv.org/content/biorxiv/early/2019/01/21/518886.full.pdf