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

作为细胞死亡信号和细胞因子表达的有力驱动因素，RIPK3在癌细胞中经常受到表观遗传学的抑制，但在纤维炎症性疾病中却被强烈诱导。我们观察到在肝纤维化的肌成纤维细胞中RIPK3的强烈上调，这一步骤通常先于肝细胞癌的发展。促纤维化的RIPK1整合素信号释放了β复合体介导的RIPK3基因的表观遗传抑制。本文拟对RIPK3在肿瘤组织中的表达进行研究，明确RIPK3在肿瘤间质和癌细胞中差异表达的分子机制，并探讨RIPK3信号轴在促结缔组织增生反应和肿瘤发生中的生物学意义。

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.