Differential regulation of RIPK3 in tumour stroma and cancer cells (P15)

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As a potent driver of cell death signalling and cytokine expression, RIPK3 is often epigenetically repressed in cancer cells but strongly induced in fibro-inflammatory diseases. We observed strong upregulation of RIPK3 in the myofibroblast compartment in liver fibrosis, a step that typically precedes the development of HCC. The upregulation of RIPK3 in desmoplastic reaction is driven by pro-fibrotic β1 integrin signalling which releases NuRD complex-mediated epigenetic repression of RIPK3 locus. Here now plan to characterize RIPK3-expressing compartments in tumour tissues, define the molecular mechanisms of differential RIPK3 expression in tumour stroma and cancer cells, and examine the biological significance of this signalling axis in desmoplastic reaction and tumour development.