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bioRxiv · 10.1101/518886

A sustained small increase in NOD1 expression promotes ligand-independent oncogenic activity

Rommereim, L. M.·Akhade, A. S.·Dutta, B.·Hutcheon, C.·Lounsbury, N. W.·Rostomily, C. C.·Savan, R.·Fraser, I. D. C.·Germain, R. N.·Subramanian, N.
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Abstract

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.\n\nOne Sentence SummaryA small change in NOD1 expression has a large cancer-promoting impact on cell state.

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Rommereim, L. M., Akhade, A. S., Dutta, B., Hutcheon, C., Lounsbury, N. W., Rostomily, C. C., Savan, R., Fraser, I. D. C., Germain, R. N., Subramanian, N.. 2019-01-21. A sustained small increase in NOD1 expression promotes ligand-independent oncogenic activity. https://doi.org/10.1101/518886

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