| Literature DB >> 34779407 |
Pavlos Missios1,2,3, Edroaldo Lummertz da Rocha1,2,3,4, Daniel S Pearson1,2,3, Julia Philipp5,6, Maria M Aleman7, Mehdi Pirouz1,2,8, Dorian Farache9,10, Joseph W Franses5, Caroline Kubaczka1,2,3, Kaloyan M Tsanov1,2,3, Deepak K Jha1,2,3, Brian Pepe-Mooney1,2, John T Powers1,2,3, Richard I Gregory1,2,3,11,12, Amy Sy Lee9,10, Daniel Dominguez7,13, David T Ting5, George Q Daley1,2,3.
Abstract
High expression of LIN28B is associated with aggressive malignancy and poor survival. Here, probing MYCN-amplified neuroblastoma as a model system, we showed that LIN28B expression was associated with enhanced cell migration in vitro and invasive and metastatic behavior in murine xenografts. Sequence analysis of the polyribosome fraction of LIN28B-expressing neuroblastoma cells revealed let-7-independent enrichment of transcripts encoding components of the translational and ribosomal apparatus and depletion of transcripts of neuronal developmental programs. We further observed that LIN28B utilizes both its cold shock and zinc finger RNA binding domains to preferentially interact with MYCN-induced transcripts of the ribosomal complex, enhancing their translation. These data demonstrated that LIN28B couples the MYCN-driven transcriptional program to enhanced ribosomal translation, thereby implicating LIN28B as a posttranscriptional driver of the metastatic phenotype.Entities:
Keywords: Cancer; Cell migration/adhesion; Oncology; Translation
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Year: 2021 PMID： 34779407 PMCID： PMC8592552 DOI： 10.1172/JCI145142
Source DB: PubMed Journal: J Clin Invest ISSN： 0021-9738 Impact factor: 14.808