Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark
Life Sci Alliance. 2019 Jul 22;2(4). doi: 10.26508/lsa.201900381. Print 2019 Aug.
One of the fundamental issues in biology is understanding how organ size is controlled. Tissue growth has to be carefully regulated to generate well-functioning organs, and defects in growth control can result in tumor formation. The Hippo signaling pathway is a universal growth regulator and has been implicated in cancer. In , the Hippo pathway acts through the miRNA to regulate cell proliferation and apoptosis. Even though the targets regulating apoptosis have been determined, the target genes controlling proliferation have not been identified thus far. In this study, we identify the gene as a direct target gene. Tribbles limits cell proliferation by suppressing G2/M transition. We show that regulation by is central in controlling tissue growth and tumorigenesis. We expand our study to other cell cycle regulators and show that deregulated G2/M transition can collaborate with oncogene activation driving tumor formation.
生物学中的一个基本问题是理解器官大小是如何控制的。组织生长必须受到严格的调控，才能产生功能正常的器官，而生长控制的缺陷可能导致肿瘤形成。Hippo 信号通路是一种普遍的生长调节剂，与癌症有关。在 中，Hippo 途径通过 miRNA 来调节细胞增殖和细胞凋亡。尽管已经确定了调节细胞凋亡的 靶点，但迄今为止尚未确定控制增殖的靶基因。在这项研究中，我们确定了基因 作为 Hippo 信号通路的一个直接靶基因。Tribbles 通过抑制 G2/M 期转换来限制细胞增殖。我们表明， 受 的调控在控制组织生长和肿瘤发生中起核心作用。我们将研究扩展到其他细胞周期调节剂，并表明失调的 G2/M 期转换可以与癌基因激活协同作用，驱动肿瘤形成。
