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dc.contributor.authorVizoso, M
dc.contributor.authorFerreira, H
dc.contributor.authorLopez-Serra, P
dc.contributor.authorCarmona, F
dc.contributor.authorMartínez-Cardús, A
dc.contributor.authorGirotti, Maria Romina
dc.contributor.authorVillanueva, A
dc.contributor.authorGuil, S
dc.contributor.authorMoutinho, C
dc.contributor.authorLiz, J
dc.contributor.authorPortela, A
dc.contributor.authorHeyn, H
dc.contributor.authorMoran, S
dc.contributor.authorVidal, A
dc.contributor.authorMartinez-Iniesta, M
dc.contributor.authorManzano, J
dc.contributor.authorFernandez-Figueras, M
dc.contributor.authorElez, E
dc.contributor.authorMuñoz-Couselo, E
dc.contributor.authorBotella-Estrada, R
dc.contributor.authorBerrocal, A
dc.contributor.authorPontén, F
dc.contributor.authorVan Den Oord, J
dc.contributor.authorGallagher, W
dc.contributor.authorFrederick, D
dc.contributor.authorFlaherty, K
dc.contributor.authorMcDermott, U
dc.contributor.authorLorigan, Paul C
dc.contributor.authorMarais, Richard
dc.contributor.authorEsteller, M
dc.date.accessioned2015-07-01T07:50:27Zen
dc.date.available2015-07-01T07:50:27Zen
dc.date.issued2015-06-01en
dc.identifier.citationEpigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR. 2015: Nat Meden
dc.identifier.issn1546-170Xen
dc.identifier.pmid26030178en
dc.identifier.doi10.1038/nm.3863en
dc.identifier.urihttp://hdl.handle.net/10541/558687en
dc.description.abstractMetastasis 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.
dc.languageENGen
dc.language.isoenen
dc.rightsArchived with thanks to Nature medicineen
dc.titleEpigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR.en
dc.typeArticleen
dc.contributor.departmentCancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, L'Hospitalet, Barcelona,en
dc.identifier.journalNature Medicineen
html.description.abstractMetastasis 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.


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