YAP/TAZ enhances P-body formation to promote tumorigenesis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39046443.
- Also identified by DOI 10.7554/eLife.88573 and PMC identifier 11268890.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 <i>SAMD4A, AJUBA</i>, and <i>WTIP</i> and transcriptional suppression of the tumor suppressor gene <i>PNRC1</i> 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 (<i>DDX6, DCP1A,</i> and <i>LSM14A</i>), we determined that disruption of P-bodies attenuates cell proliferation, cell migration, and tumor growth induced by overexpression of YAP<sup>5SA</sup> 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 <i>SAMD4A, AJUBA, WTIP, PNRC1,</i> 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.
Medical subject headings
- YAP-Signaling Proteins
- Adaptor Proteins, Signal Transducing
- Transcription Factors
- Carcinogenesis
- Transcriptional Coactivator with PDZ-Binding Motif Proteins
- Trans-Activators