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

RIPK3 在肿瘤基质和癌细胞中的差异调节 (P15)

• 批准号: 405444248
• 金额: --
• 依托单位: Genzentrum - Laboratorium für molekulare Biologie
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/405444248?language=en
• 关键词: Differential; regulation; RIPK3; tumour; stroma

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.

作为细胞死亡信号传导和细胞因子表达的有效驱动因子，RIPK3通常在癌细胞中被表观遗传抑制，但在纤维炎性疾病中被强烈诱导。我们观察到肝纤维化中肌成纤维细胞隔室中RIPK3的强烈上调，这是HCC发展之前的一个典型步骤。促纤维增生反应中RIPK 3的上调是由促纤维化β1整合素信号传导驱动的，该信号传导释放了NuRD复合物介导的RIPK 3基因座的表观遗传抑制。在这里，现在计划描述肿瘤组织中RIPK3表达区室的特征，确定肿瘤基质和癌细胞中RIPK3差异表达的分子机制，并检查该信号传导轴在促纤维增生反应和肿瘤发展中的生物学意义。