Identification and characterization of novel gene networks connecting cancer and aging

连接癌症和衰老的新基因网络的鉴定和表征

• 批准号: 220520641
• 负责人: Dr. Tobias Reiff
• 金额: --
• 依托单位: Institut für Genetik
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/220520641?language=en
• 关键词: Identification; characterization; novel; gene; networks

Adult stem cells are exposed to environmental stress and intracellular damages that go together with the process of aging. Longevity seems to be associated with increased renewal capacity via stem cells but also with increased cancer risk. In contrast, aging is associated with disturbance in stem cell number or function. This trade-off between longevity (aging) and cancer is further strengthened by findings that several solid cancer types harbor cancer stem cells that may derive from normal stem- or progenitor cells. Cancer stem cells are likely to contribute to therapy resistance and tumor relapse. This fellowship proposal stems from the identification of two aging-related genes Indy and krüppel homolog 1 (kr-h1) as enhancers of malignant growth in a high throughput unbiased gain-of-expression genetic screen in Drosophila. I noted that flies bearing kr-h1-induced tumors die 24 hours after eclosion with defects reminiscent to aged flies. The proposed work aims to identify the mechanism behind these observations using well-established Drosophila genetics, molecular biology and biochemistry. Particularly, I intend to take advantage of quantitative mass spectrometry and propose to identify, through genome and proteome-wide analyses, Indy and/or kr-h1 gene networks that have differential function or expression in young and aged flies in stem cell compartments. Results from quantitative mass spectrometry will be further investigated in a Drosophila tumor paradigm and in human cancer cells. These studies will help to identify common networks of the currently separated research fields of aging and cancer.

成体干细胞暴露于环境压力和细胞内损伤，这些损伤与衰老过程一起发生。长寿似乎与通过干细胞增加的更新能力有关，但也与癌症风险增加有关。相反，衰老与干细胞数量或功能的紊乱有关。长寿（衰老）和癌症之间的这种权衡进一步加强了几种实体癌症类型含有可能来自正常干细胞或祖细胞的癌症干细胞的发现。癌症干细胞可能导致治疗抵抗和肿瘤复发。这项奖学金的建议源于两个衰老相关基因Indy和krüppel同源物1（kr-h1）的鉴定，作为果蝇中高通量无偏表达获得性遗传筛选的恶性生长增强剂。我注意到，带有kr-h1诱导肿瘤的果蝇在羽化后24小时死亡，其缺陷让人想起老年果蝇。拟议的工作旨在利用完善的果蝇遗传学，分子生物学和生物化学来确定这些观察结果背后的机制。特别是，我打算利用定量质谱，并建议确定，通过基因组和蛋白质组范围内的分析，Indy和/或kr-h1基因网络，具有不同的功能或表达在年轻和老年苍蝇的干细胞室。定量质谱的结果将在果蝇肿瘤范例和人类癌细胞中进一步研究。这些研究将有助于确定目前分离的衰老和癌症研究领域的共同网络。