Two Isoforms of the Guanine Nucleotide Exchange Factor, Daple/CCDC88C Cooperate as Tumor Suppressors
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Identificadores![](/xmlui/themes/Mirage2//images/despl_identif.png)
Identificadores
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Fecha de publicación
2019Título de revista
Scientific Reports
Tipo de contenido
Artigo
DeCS
ARN | unión proteica | animales | genes | humanos | células COS | estudios de cohortes | células 3T3 NIH | ratones | células HeLaMeSH
Humans | Genes | HeLa Cells | COS Cells | RNA | Mice | Animals | Protein Binding | Cohort Studies | NIH 3T3 CellsResumen
Previously, Aznar et al., showed that Daple/CCDC88C enables Wnt receptors to transactivate trimeric G-proteins during non-canonical Wnt signaling via a novel G-protein binding and activating (GBA) motif. By doing so, Daple serves two opposing roles; earlier during oncogenesis it suppresses neoplastic transformation and tumor growth, but later it triggers epithelial-to-mesenchymal-transition (EMT). We have identified and characterized two isoforms of the human Daple gene. While both isoforms cooperatively suppress tumor growth via their GBA motif, only the full-length transcript triggers EMT and invasion. Both isoforms are suppressed during colon cancer progression, and their reduced expression carries additive prognostic significance. These findings provide insights into the opposing roles of Daple during cancer progression and define the G-protein regulatory GBA motif as one of the minimal modules essential for Daple's role as a tumor suppressor.
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