Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR
| Autor: | Fredrik Pontén, Rafael Botella-Estrada, Miguel Vizoso, Ultan McDermott, Jose Luis Manzano, Anna Martínez-Cardús, Catia Moutinho, Joost van den Oord, María Martínez-Iniesta, Alberto Villanueva, Paula Lopez-Serra, August Vidal, Sebastian Moran, Elena Elez, F. Javier Carmona, Julia Liz, Maria Romina Girotti, Holger Heyn, Sonia Guil, Alfonso Berrocal, Paul Lorigan, Dennie T. Frederick, María Teresa Fernández-Figueras, Humberto J. Ferreira, Anna Portela, William M. Gallagher, Richard Marais, Eva Muñoz-Couselo, Keith T. Flaherty, Manel Esteller |
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| Přispěvatelé: | Universitat de Barcelona |
| Rok vydání: | 2015 |
| Předmět: |
Transcriptional Activation
GTPase-activating protein Immunoprecipitation Mice Nude Editorials: Cell Cycle Features Biology Bioinformatics Methylation General Biochemistry Genetics and Molecular Biology Epigenesis Genetic Metastasis Epigènesi Metàstasi Cell Line Tumor medicine Animals Protein Isoforms RNA Messenger Epigenetics Neoplasm Metastasis RNA Small Interfering Promoter Regions Genetic Proteïnes supressores de tumors Protein Kinase Inhibitors Melanoma GTPase-Activating Proteins General Medicine DNA Methylation Prognosis medicine.disease Tumor suppressor protein ErbB Receptors Molecular Weight Treatment Outcome rab GTP-Binding Proteins DNA methylation Disease Progression Cancer research Rab Metilació Protein Binding Signal Transduction Epigenesis |
| Zdroj: | Recercat. Dipósit de la Recerca de Catalunya instname Dipòsit Digital de la UB Universidad de Barcelona Cell Cycle NATURE MEDICINE r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe Europe PubMed Central |
| ISSN: | 1546-170X 1078-8956 |
| Popis: | Metastasis is respoMetastasis is responsible for most cancer-related deaths, and, among common tumor types, melanoma is one with great potential to metastasize. Here we study the contribution of epigenetic changes to the dissemination process by analyzing the changes that occur at the DNA methylation level between primary cancer cells and metastases. We found a hypomethylation event that reactivates a cryptic transcript of the Rab GTPase activating protein TBC1D16 (TBC1D16-47 kDa; referred to hereafter as TBC1D16-47KD) to be a characteristic feature of the metastatic cascade. This short isoform of TBC1D16 exacerbates melanoma growth and metastasis both in vitro and in vivo. By combining immunoprecipitation and mass spectrometry, we identified RAB5C as a new TBC1D16 target and showed that it regulates EGFR in melanoma cells. We also found that epigenetic reactivation of TBC1D16-47KD is associated with poor clinical outcome in melanoma, while conferring greater sensitivity to BRAF and MEK inhibitors. |
| Databáze: | OpenAIRE |
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