Nuclear FAK and Runx1 Cooperate to Regulate IGFBP3, Cell-Cycle Progression, and Tumor Growth.
Nuclear FAK and Runx1 Cooperate to Regulate IGFBP3, Cell-Cycle Progression, and Tumor Growth.
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核 FAK 和 Runx1 协同调节 IGFBP3、细胞周期进展和肿瘤生长。
DOI：
10.1158/0008-5472.can-17-0418
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发表时间：
2017-10-01
期刊：
影响因子：
11.2
通讯作者：
Serrels A
中科院分区：
文献类型：
--
作者：
Canel M;Byron A;Sims AH;Cartier J;Patel H;Frame MC;Brunton VG;Serrels B;Serrels A
核局灶黏附激酶（FAK）是癌症中潜在的重要基因表达调节剂，影响细胞功能和肿瘤周围微环境的组成。在此，我们在小鼠皮肤鳞状细胞癌（SCC）模型中报道，核FAK调节胰岛素样生长因子结合蛋白3 （IGFBP3）的runx1依赖性转录，并在体内调节SCC细胞周期进展和肿瘤生长。此外，我们在SCC细胞的细胞核中发现了FAK和Runx1之间的一个新的分子复合物，并表明FAK与许多Runx1调节蛋白相互作用，包括Sin3a和其他已知通过翻译后修饰改变Runx1转录功能的表观遗传修饰因子。这些发现为FAK在调节基因转录的分子复合物中作为支架蛋白的作用提供了重要的新见解。
Nuclear focal adhesion kinase (FAK) is a potentially important regulator of gene expression in cancer, impacting both cellular function and the composition of the surrounding tumor microenvironment. Here we report in a murine model of skin squamous cell carcinoma (SCC) that nuclear FAK regulates Runx1-dependent transcription of insulin-like growth factor binding protein 3 (IGFBP3), and that this regulates SCC cell cycle progression and tumor growth in vivo. Furthermore, we identified a novel molecular complex between FAK and Runx1 in the nucleus of SCC cells and showed that FAK interacted with a number of Runx1 regulatory proteins, including Sin3a and other epigenetic modifiers known to alter Runx1 transcriptional function through post-translational modification. These findings provide important new insights into the role of FAK as a scaffolding protein in molecular complexes that regulate gene transcription.