Two Isoforms of the Guanine Nucleotide Exchange Factor, Daple/CCDC88C Cooperate as Tumor Suppressors
Year: 2019
Type: article
Abstract: 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.
Source: Scientific Reports
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,790
Funders: U.S. Department of Health and Human Services, American Cancer Society, Georgia Clinical and Translational Science Alliance, Moores Cancer Center, UC San Diego Health, Bundesministerium für Bildung und Forschung, Ministerio de Educación, Cultura y Deporte, National Institutes of Health, University of California, San Diego, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences
Awards: G1081931513, G1461477048, G1474206309, G1638849993, G1760674687, G2255625076, G2478754673, G3410713429, G3411000325, G3686159151, G3880607359, G3989252317, G4787607065, G5184084544, G5568180862, G6626256576, G8832445876, G9000034993, G9000131308, G9000140428, G9000188019, G9000292485, G9000351709, Cancer Biology, Informatics & Omics (CBIO) Training Program, Modulation of G proteins by Growth Factors
OpenAlex ID: W2969952023