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结直肠癌中 Wnt/β-连环蛋白通路的转录调控。

Transcriptional Regulation of Wnt/β-Catenin Pathway in Colorectal Cancer.

机构信息

Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia.

Department of Molecular and Translational Science, Monash University, Clayton, VIC 3800, Australia.

出版信息

Cells. 2020 Sep 19;9(9):2125. doi: 10.3390/cells9092125.

Abstract

The Wnt/β-catenin signaling pathway exerts integral roles in embryogenesis and adult homeostasis. Aberrant activation of the pathway is implicated in growth-associated diseases and cancers, especially as a key driver in the initiation and progression of colorectal cancer (CRC). Loss or inactivation of Adenomatous polyposis coli (APC) results in constitutive activation of Wnt/β-catenin signaling, which is considered as an initiating event in the development of CRC. Increased Wnt/β-catenin signaling is observed in virtually all CRC patients, underscoring the importance of this pathway for therapeutic intervention. Prior studies have deciphered the regulatory networks required for the cytoplasmic stabilisation or degradation of the Wnt pathway effector, β-catenin. However, the mechanism whereby nuclear β-catenin drives or inhibits expression of Wnt target genes is more diverse and less well characterised. Here, we describe a brief synopsis of the core canonical Wnt pathway components, set the spotlight on nuclear mediators and highlight the emerging role of chromatin regulators as modulators of β-catenin-dependent transcription activity and oncogenic output.

摘要

Wnt/β-catenin 信号通路在胚胎发生和成人稳态中发挥着重要作用。该通路的异常激活与生长相关疾病和癌症有关,特别是作为结直肠癌 (CRC) 起始和进展的关键驱动因素。腺瘤性结肠息肉病 (APC) 的缺失或失活导致 Wnt/β-catenin 信号通路的持续激活,这被认为是 CRC 发展的起始事件。几乎所有 CRC 患者都观察到 Wnt/β-catenin 信号的增加,这突显了该通路在治疗干预中的重要性。先前的研究已经阐明了细胞质稳定或降解 Wnt 通路效应物 β-catenin 所需的调控网络。然而,核 β-catenin 驱动或抑制 Wnt 靶基因表达的机制更加多样化,也不太为人所知。在这里,我们简要概述了核心经典 Wnt 通路成分,将重点放在核介质上,并强调染色质调节剂作为 β-catenin 依赖性转录活性和致癌输出调节剂的新兴作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ac8/7564852/0c27f1d2d25a/cells-09-02125-g001.jpg

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