RT Journal Article SR Electronic T1 A sustained small increase in NOD1 expression promotes ligand-independent oncogenic activity JF bioRxiv FD Cold Spring Harbor Laboratory SP 518886 DO 10.1101/518886 A1 Leah M. Rommereim A1 Ajay Suresh Akhade A1 Bhaskar Dutta A1 Carolyn Hutcheon A1 Nicolas W. Lounsbury A1 Clifford C. Rostomily A1 Ram Savan A1 Iain D. C. Fraser A1 Ronald N. Germain A1 Naeha Subramanian YR 2019 UL http://biorxiv.org/content/early/2019/01/21/518886.abstract 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.