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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
Proteïnes supressores de tumors
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:
It is part of: Nature Medicine, 2015, vol. 21, num. 7, p. 741-750
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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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