Fra-1: a safeguard protecting tumor cells from oncogenic stress

Fra-1：保护肿瘤细胞免受致癌应激的保障

• 批准号: 409543862
• 负责人: Professor Dr. Günter Schneider
• 金额: --
• 依托单位: Klinik für Allgemein-, Viszeral- und Kinderchirurgie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/409543862?language=en
• 关键词: Fra; safeguard; protecting; tumor; cells

Across species and tumors our preliminary data provide robust evidence for the co-selection/co-expression of the transcription factors Fra-1, a member of the AP-1 family, and MYC, an oncogene with relevance for most cancers, especially in context of oncogenic KRAS. Therefore, we hypothesize that Fra-1 is a "safeguard" needed in tumor cells with supra-physiological MYC activity to cope with MYC-dependent oncogenic stress pathways. Using PDAC as a bona fide KRAS-driven cancer, we aim to decipher and understand the function of Fra-1 and elucidate how Fra-1 protects against MYC-dependent oncogenic stress. Since context matters, we will also analyze whether the molecular functions detected in KRAS-driven PDAC is evident in KRAS-driven NSCLC models. We propose that the detailed understanding of Fra-1 will allow to develop novel therapeutic concepts for a subtype of KRAS-driven cancers by the targeting of "safeguard" functions of Fra-1, which we plan to test in up-to-date human model systems of PDAC.

在物种和肿瘤中，我们的初步数据为转录因子Fra-1（AP-1家族成员）和MYC（与大多数癌症相关的癌基因）的共选择/共表达提供了有力的证据，特别是在致癌KRAS的背景下。因此，我们假设Fra-1是具有超生理MYC活性的肿瘤细胞所需的“保护”，以科普MYC依赖的致癌应激途径。使用PDAC作为真正的KRAS驱动的癌症，我们的目标是破译和理解Fra-1的功能，并阐明Fra-1如何保护免受MYC依赖的致癌应激。由于背景很重要，我们还将分析在KRAS驱动的PDAC中检测到的分子功能是否在KRAS驱动的NSCLC模型中是明显的。我们建议，对Fra-1的详细了解将允许通过靶向Fra-1的“保护”功能来开发KRAS驱动的癌症亚型的新治疗概念，我们计划在最新的PDAC人类模型系统中进行测试。