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胃癌细胞中YAP和TAZ常见和独特的转录特征

Common and Unique Transcription Signatures of YAP and TAZ in Gastric Cancer Cells.

作者信息

Lee Yaelim, Finch-Edmondson Megan, Cognart Hamizah, Zhu Bowen, Song Haiwei, Low Boon Chuan, Sudol Marius

机构信息

Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.

Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore.

出版信息

Cancers (Basel). 2020 Dec 7;12(12):3667. doi: 10.3390/cancers12123667.

Abstract

YAP and its paralog TAZ are the nuclear effectors of the Hippo tumour-suppressor pathway, and function as transcriptional co-activators to control gene expression in response to mechanical cues. To identify both common and unique transcriptional targets of YAP and TAZ in gastric cancer cells, we carried out RNA-sequencing analysis of overexpressed YAP or TAZ in the corresponding paralogous gene-knockouts (KOs), TAZ KO or YAP KO, respectively. Gene Ontology (GO) analysis of the YAP/TAZ-transcriptional targets revealed activation of genes involved in platelet biology and lipoprotein particle formation as targets that are common for both YAP and TAZ. However, the GO terms for cell-substrate junction were a unique function of YAP. Further, we found that YAP was indispensable for the gastric cancer cells to re-establish cell-substrate junctions on a rigid surface following prolonged culture on a soft substrate. Collectively, our study not only identifies common and unique transcriptional signatures of YAP and TAZ in gastric cancer cells but also reveals a dominant role for YAP over TAZ in the control of cell-substrate adhesion.

摘要

YAP及其旁系同源物TAZ是Hippo肿瘤抑制途径的核效应因子,作为转录共激活因子,响应机械信号控制基因表达。为了鉴定胃癌细胞中YAP和TAZ共同的和独特的转录靶点,我们分别在相应的旁系同源基因敲除(KO)细胞系(TAZ KO或YAP KO)中对过表达的YAP或TAZ进行了RNA测序分析。对YAP/TAZ转录靶点的基因本体(GO)分析显示,参与血小板生物学和脂蛋白颗粒形成的基因被激活,这些是YAP和TAZ共有的靶点。然而,细胞-底物连接的GO术语是YAP的独特功能。此外,我们发现,在软基质上长时间培养后,胃癌细胞在刚性表面重新建立细胞-底物连接时,YAP是不可或缺的。总之,我们的研究不仅鉴定了胃癌细胞中YAP和TAZ共同的和独特的转录特征,还揭示了在控制细胞-底物黏附中,YAP比TAZ发挥更主要的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfec/7762230/dff375477feb/cancers-12-03667-g001.jpg

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