Shen Xia, Peng Xiang, Guo YueGui, Dai Zhujiang, Cui Long, Yu Wei, Liu Yun, Liu Chen-Ying
Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Colorectal Cancer Research Center, Shanghai, China.
Elife. 2024 Jul 24;12:RP88573. doi: 10.7554/eLife.88573.
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.
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。