PT - JOURNAL ARTICLE AU - Leah M. Rommereim AU - Ajay Suresh Akhade AU - Bhaskar Dutta AU - Carolyn Hutcheon AU - Nicolas W. Lounsbury AU - Clifford C. Rostomily AU - Ram Savan AU - Iain D. C. Fraser AU - Ronald N. Germain AU - Naeha Subramanian TI - A sustained small increase in NOD1 expression promotes ligand-independent oncogenic activity AID - 10.1101/518886 DP - 2019 Jan 01 TA - bioRxiv PG - 518886 4099 - http://biorxiv.org/content/early/2019/01/21/518886.short 4100 - http://biorxiv.org/content/early/2019/01/21/518886.full AB - 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.