Data from Pooled CRISPR Screening Identifies P-Bodies as Repressors of Cancer Epithelial–Mesenchymal Transition

• DOI: 10.1158/0008-5472.c.7104597.v1
• Publication Date: 2024-03-04T22:25:42Z
• Authors: Liang Fang; Li Zhang; Mengran Wang; Yuhao He; Jiao Yang; Zengjin Huang; Ying Tan; Ke Fang; Jun Li; Zhiyuan Sun; Yanping Li; Yisen Tang; Weizheng Liang; Huanhuan Cui; Qionghua Zhu; Zhe Wu; Yiming Li; Yuhui Hu; Wei Chen

<div>Abstract<p>Epithelial–mesenchymal transition (EMT) is a fundamental cellular process frequently hijacked by cancer cells to promote tumor progression, especially metastasis. EMT orchestrated complex molecular network acting at different layers of gene regulation. In addition transcriptional regulation, posttranscriptional mechanisms may also play role in EMT. Here, we performed pooled CRISPR screen analyzing the influence 1,547 RNA-binding proteins on cell motility colon and identified multiple core components P-bodies (PB) as negative modulators migration. Further experiments demonstrated that PB depletion silencing DDX6 or EDC4 could activate hallmarks thereby enhancing migration <i>in vitro</i> well metastasis formation vivo</i>. Integrative multiomics analysis revealed PBs repress translation driver HMGA2, which contributed PB-meditated regulation This mechanism conserved other types. Furthermore, endoplasmic reticulum stress was an intrinsic signal induced disassembly translational derepression HMGA2. Taken together, this study has function cancer.</p>Significance:<p>Systematic investigation established connection between P-body–mediated control EMT, be therapeutically exploited attenuate formation.</p></div>