Basti Alireza, Fior Rita, Yalҫin Müge, Póvoa Vanda, Astaburuaga Rosario, Li Yin, Naderi Julian, Godinho Ferreira Miguel, Relógio Angela
Institute for Theoretical Biology (ITB), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
Molecular Cancer Research Center (MKFZ), Medical Department of Hematology, Oncology, and Tumor Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
Cancers (Basel). 2020 Apr 1;12(4):853. doi: 10.3390/cancers12040853.
Malfunctions of circadian clock trigger abnormal cellular processes and influence tumorigenesis. Using an and xenograft model, we show that circadian clock disruption via the downregulation of the core-clock genes , , and impacts the circadian phenotype of , , and , and affects proliferation, apoptosis, and cell migration. In particular, both our and results suggest an impairment of cell motility and a reduction in micrometastasis formation upon knockdown of , accompanied by altered expression levels of and . Interestingly we show that differential proliferation and reduced tumour growth may be due to the additional influence of the host-clock and/or to the 3D tumour architecture. Our results raise new questions concerning host-tumour interaction and show that core-clock genes are involved in key cancer properties, including the regulation of cell migration and invasion by in zebrafish xenografts.
生物钟功能失调会引发异常的细胞过程并影响肿瘤发生。利用 和 异种移植模型，我们发现通过下调核心生物钟基因 、 和 导致的生物钟紊乱会影响 、 和 的生物钟表型，并影响细胞增殖、凋亡和迁移。特别是，我们的 和 结果均表明，敲低 后细胞运动能力受损，微转移形成减少，同时 和 的表达水平发生改变。有趣的是，我们发现增殖差异和肿瘤生长减缓可能归因于宿主生物钟的额外影响和/或三维肿瘤结构。我们的结果提出了关于宿主与肿瘤相互作用的新问题，并表明核心生物钟基因参与了关键的癌症特性，包括斑马鱼异种移植中 对细胞迁移和侵袭的调控。
