Two Isoforms of the Guanine Nucleotide Exchange Factor, Daple/CCDC88C Cooperate as Tumor Suppressors
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 neoplasti...
| Autores: | , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Servizo Galego de Saúde (SERGAS) |
| Repositorio: | RUNA. Repositorio da Consellería de Sanidade e Sergas |
| OAI Identifier: | oai:runa.sergas.gal:20.500.11940/15427 |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pubmed/31431650 http://hdl.handle.net/20.500.11940/15427 |
| Access Level: | acceso abierto |
| Palabra clave: | Humans Genes HeLa Cells COS Cells RNA Mice Animals Protein Binding Cohort Studies NIH 3T3 Cells ARN unión proteica animales genes humanos células COS estudios de cohortes células 3T3 NIH ratones células HeLa CHUS IDIS |
| Sumario: | 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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