Pooled CRISPR Screening Identifies P-Bodies as Repressors of Cancer Epithelial-Mesenchymal Transition.
Liang FangLi ZhangMengran WangYuhao HeJiao YangZengjin HuangYing TanKe FangJun LiZhiyuan SunYanping LiYisen TangWeizheng LiangHuanhuan CuiQionghua ZhuZhe WuYiming LiYuhui HuWei ChenPublished in: Cancer research (2024)
Epithelial-mesenchymal transition (EMT) is a fundamental cellular process frequently hijacked by cancer cells to promote tumor progression, especially metastasis. EMT is orchestrated by a complex molecular network acting at different layers of gene regulation. In addition to transcriptional regulation, post-transcriptional mechanisms may also play a role in EMT. Here, we performed a pooled CRISPR screen analyzing the influence of 1547 RNA binding proteins (RBPs) on cell motility in colon cancer cells and identified multiple core components of P-bodies (PBs) as negative modulators of cancer cell migration. Further experiments demonstrated that PB depletion by silencing DDX6 or EDC4 could activate hallmarks of EMT thereby enhancing cell migration in vitro as well as metastasis formation in vivo. Integrative multi-omics analysis revealed that PBs could repress the translation of the EMT-driver gene HMGA2, which contributed to PB-meditated regulation of EMT. This mechanism is conserved in other cancer types. Furthermore, endoplasmic reticulum (ER) stress was an intrinsic signal that induced PB disassembly and translational derepression of HMGA2. Taken together, this study has identified a function of PBs in regulation of EMT in cancer.
Keyphrases
- epithelial mesenchymal transition
- cell migration
- papillary thyroid
- transforming growth factor
- signaling pathway
- squamous cell
- genome wide
- single cell
- heavy metals
- randomized controlled trial
- transcription factor
- gene expression
- escherichia coli
- dna methylation
- clinical trial
- risk assessment
- childhood cancer
- diabetic rats
- single molecule
- long non coding rna
- data analysis
- open label