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YAP/TAZ增强P小体形成以促进肿瘤发生。

YAP/TAZ enhances P-body formation to promote tumorigenesis.

作者信息

Shen Xia, Peng Xiang, Guo YueGui, Dai Zhujiang, Cui Long, Yu Wei, Liu Yun, Liu Chen-Ying

机构信息

Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Shanghai Colorectal Cancer Research Center, Shanghai, China.

出版信息

Elife. 2024 Jul 24;12:RP88573. doi: 10.7554/eLife.88573.

Abstract

The role of processing bodies (P-bodies) in tumorigenesis and tumor progression is not well understood. Here, we showed that the oncogenes YAP/TAZ promote P-body formation in a series of cancer cell lines. Mechanistically, both transcriptional activation of the P-body-related genes , and and transcriptional suppression of the tumor suppressor gene are involved in enhancing the effects of YAP/TAZ on P-body formation in colorectal cancer (CRC) cells. By reexpression of PNRC1 or knockdown of P-body core genes ( and ), we determined that disruption of P-bodies attenuates cell proliferation, cell migration, and tumor growth induced by overexpression of YAP in CRC. Analysis of a pancancer CRISPR screen database (DepMap) revealed co-dependencies between YAP/TEAD and the P-body core genes and correlations between the mRNA levels of and YAP target genes. Our study suggests that the P-body is a new downstream effector of YAP/TAZ, which implies that reexpression of PNRC1 or disruption of P-bodies is a potential therapeutic strategy for tumors with active YAP.

摘要

加工小体(P小体)在肿瘤发生和肿瘤进展中的作用尚未完全明确。在此,我们发现癌基因YAP/TAZ在一系列癌细胞系中促进P小体形成。从机制上讲,P小体相关基因的转录激活以及肿瘤抑制基因的转录抑制均参与增强YAP/TAZ对结直肠癌(CRC)细胞中P小体形成的影响。通过重新表达PNRC1或敲低P小体核心基因( 和 ),我们确定破坏P小体可减弱CRC中YAP过表达诱导的细胞增殖、细胞迁移和肿瘤生长。对泛癌CRISPR筛选数据库(DepMap)的分析揭示了YAP/TEAD与P小体核心基因之间的共同依赖性以及 和YAP靶基因mRNA水平之间的相关性。我们的研究表明,P小体是YAP/TAZ的一种新的下游效应物,这意味着重新表达PNRC1或破坏P小体是针对YAP活性高的肿瘤的一种潜在治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba7/11268890/42bc39d0955d/elife-88573-fig1.jpg

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