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Highlight: RNA-binding proteins in cancer

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Sci. Signal.  19 Sep 2017:
Vol. 10, Issue 497, eaap9424
DOI: 10.1126/scisignal.aap9424

ADAR promotes lung adenocarcinoma migration and invasion through stabilization of FAK.

An increasing number of papers and reviews are implicating RNA-binding proteins (RNA-BPs) as modulators of cancer progression and therapeutic response. In this issue of Science Signaling, Amin and colleagues show that tumor expression of the gene encoding the RNA-BP ADAR1, an isoform of adenosine deaminase acting on double-stranded RNA, correlates with tumor recurrence, progression, and poor prognosis in patients with stage 1 lung adenocarcinoma. Remarkably, ADAR1 expression modulated the actin cytoskeleton, invasive potential, and mesenchymal phenotype in lung adenocarcinoma cells. The underlying molecular mechanism turns out to involve ADAR1-mediated editing of the mRNA of a critical adenosine within an intron of the cytoplasmic cytoskeletal kinase FAK, converting it to an inosine, and resulting in increased FAK mRNA stabilization and increased levels of FAK activity. A significant fraction of the invasive potential of ADAR1 knockdown cells could be restored by exogenous expression of FAK, validating that FAK is one of the key ADAR1 targets that likely controls tumor migration and metastasis. Whether the increased FAK mRNA stabilization through an intronic editing event also enhances its splicing was not directly investigated. This paper, which links a specific RNA-BP to clinical outcome in lung cancer, adds to the emerging evidence that RNA-BPs are key controllers of tumor biology.

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