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http://hdl.handle.net/2445/110925
Title: | Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR |
Author: | Vizoso, Miguel Ferreira, Humberto J. López Serra, Paula Carmona, F. Javier Martínez Cardús, Anna Girotti, Maria Romina Villanueva Garatachea, Alberto Guil, Sonia Moutinho, Cátia Liz, Julia Portela, Anna Heyn, Holger Moran, Sebastian Vidal-Bel, August Martínez Iniesta, María Manzano, José Luis Fernandez-Figueras, Maria Teresa Élez, Elena Muñoz-Couselo, Eva Botella-Estrada, Rafael Berrocal, Alfonso Pontén, Fredrik Oord, Joost van den Gallagher, William M. DenFrederick, Dennie T. Flaherty, Keith T. McDermott, Ultan Lorigan, Paul Marais, Richard Esteller, Manel |
Keywords: | Melanoma Metàstasi Epigènesi Metilació Proteïnes supressores de tumors Melanoma Metastasis Epigenesis Methylation Tumor suppressor protein |
Issue Date: | 1-Jun-2015 |
Publisher: | Nature Publishing Group |
Abstract: | 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. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1038/nm.3863 |
It is part of: | Nature Medicine, 2015, vol. 21, num. 7, p. 741-750 |
URI: | http://hdl.handle.net/2445/110925 |
Related resource: | https://doi.org/10.1038/nm.3863 |
ISSN: | 1078-8956 |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Patologia i Terapèutica Experimental) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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