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Título:	Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR
Autor/a:	Vizoso, Miguel; Ferreira, Humberto J.; Lopez-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; Martinez-Iniesta, María; Manzano, Jose 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
Otros autores:	Universitat de Barcelona
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.
Materia(s):	-Melanoma -Metàstasi -Epigènesi -Metilació -Proteïnes supressores de tumors -Melanoma -Metastasis -Epigenesis -Methylation -Tumor suppressor protein
Derechos:	(c) Vizoso, Miguel et al., 2015
Tipo de documento:	Artículo Artículo - Versión aceptada
Editor:	Nature Publishing Group
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