YAP/TAZ enhances P-body formation to promote tumorigenesis

• Published in: eLife 2024-07, Vol.12
• Main Authors: Shen, Xia, Peng, Xiang, Guo, YueGui, Dai, Zhujiang, Cui, Long, Yu, Wei, Liu, Yun, Liu, Chen-Ying
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Analysis; Animals; Biosynthesis; Breast cancer; Cancer Biology; Carcinogenesis - genetics; Cell activation; Cell Line, Tumor; Cell migration; Cell Movement; Cell Proliferation; Cells; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; CRISPR; Development and progression; Gene Expression Regulation, Neoplastic; Genes; Genetic aspects; Genetic transcription; Hippo pathway; Humans; LIM Domain Proteins; Mice; Ontology; P-body; Phosphoproteins - genetics; Phosphoproteins - metabolism; PNRC1; RNA; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription activation; Transcription Factors - genetics; Transcription Factors - metabolism; Transcriptional Coactivator with PDZ-Binding Motif Proteins - metabolism; Tumor cell lines; Tumor suppressor genes; Tumorigenesis; Tumors; YAP-Signaling Proteins - genetics; YAP-Signaling Proteins - metabolism; YAP/TAZ; Yes-associated protein
• ISSN: 2050-084X; 2050-084X
• 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.