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oai:recercat.cat:2445/1109252026-03-25T05:42:15Zcom_2072_1057col_2072_478799col_2072_478916col_2072_478917col_2072_478929

00925njm 22002777a 4500 dc Vizoso, Miguel author Ferreira, Humberto J. author López Serra, Paula author Carmona, F. Javier author Martínez Cardús, Anna author Girotti, Maria Romina author Villanueva Garatachea, Alberto author Guil, Sonia author Moutinho, Cátia author Liz, Julia author Portela, Anna author Heyn, Holger author Moran, Sebastian author Vidal-Bel, August author Martínez Iniesta, María author Manzano, José Luis author Fernandez-Figueras, Maria Teresa author Élez, Elena author Muñoz-Couselo, Eva author Botella Estrada, Rafael author Berrocal, Alfonso author Pontén, Fredrik author Oord, Joost van den author Gallagher, William M. author DenFrederick, Dennie T. author Flaherty, Keith T. author McDermott, Ultan author Lorigan, Paul author Marais, Richard author Esteller, Manel, 1968- author 2017-05-12T10:22:40Z 2017-05-12T10:22:40Z 2015-06-01 2017-05-12T10:22:40Z 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. Melanoma Metàstasi Epigènesi Metilació Proteïnes supressores de tumors Melanoma Metastasis Epigenesis Methylation Tumor suppressor protein Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR