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抑制 的生长和肿瘤形成。

suppresses growth and tumor formation in .

机构信息

Department of Cellular and Molecular Medicine, University of Copenhagen, 2200N Copenhagen, Denmark.

Department of Cellular and Molecular Medicine, University of Copenhagen, 2200N Copenhagen, Denmark

出版信息

Proc Natl Acad Sci U S A. 2019 Jul 9;116(28):14055-14064. doi: 10.1073/pnas.1816981116. Epub 2019 Jun 24.

Abstract

Wnt/Wingless (Wg) signaling controls many aspects of animal development and is deregulated in different human cancers. The transcription factor dTcf/Pangolin (Pan) is the final effector of the Wg pathway in and has a dual role in regulating the expression of Wg target genes. In the presence of Wg, dTcf/Pan interacts with β-catenin/Armadillo (Arm) and induces the transcription of Wg targets. In absence of Wg, dTcf/Pan partners with the transcriptional corepressor TLE/Groucho (Gro) and inhibits gene expression. Here, we use the wing imaginal disk of as a model to examine the functions that dTcf/Pan plays in a proliferating epithelium. We report a function of dTcf/Pan in growth control and tumorigenesis. Our results show that dTcf/Pan can limit tissue growth in normal development and suppresses tumorigenesis in the context of oncogene up-regulation. We identify the conserved transcription factors () and () as genes controlled by dTcf/Pan involved in tumor development. In conclusion, this study reports a role for dTcf/Pan as a repressor of normal and oncogenic growth and identifies the genes inducing tumorigenesis downstream of dTcf/Pan.

摘要

Wnt/Wingless(Wg)信号通路控制着动物发育的许多方面,并且在不同的人类癌症中失调。转录因子 dTcf/Pangolin(Pan)是 Wg 通路在 中的最终效应物,在调节 Wg 靶基因的表达中具有双重作用。在 Wg 的存在下,dTcf/Pan 与 β-catenin/Armadillo(Arm)相互作用,并诱导 Wg 靶基因的转录。在没有 Wg 的情况下,dTcf/Pan 与转录共抑制因子 TLE/Groucho(Gro)结合,抑制基因表达。在这里,我们使用 的翅膀 imaginal 盘作为模型,研究 dTcf/Pan 在增殖上皮中发挥的功能。我们报告了 dTcf/Pan 在生长控制和肿瘤发生中的作用。我们的结果表明,dTcf/Pan 可以限制正常发育中的组织生长,并抑制致癌基因上调时的肿瘤发生。我们确定了保守的转录因子 ()和 ()作为受 dTcf/Pan 控制的参与肿瘤发生的基因。总之,这项研究报告了 dTcf/Pan 作为正常和致癌生长的抑制剂的作用,并确定了 dTcf/Pan 下游诱导肿瘤发生的基因。

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