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2015-06-01

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/110925

Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR

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https://doi.org/10.1038/nm.3863

Resum

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.

Matèries

Melanoma, Metàstasi, Epigènesi, Metilació, Proteïnes supressores de tumors

Matèries (anglès)

Melanoma, Metastasis, Epigenesis, Methylation, Tumor suppressor protein

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Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Patologia i Terapèutica Experimental)

Citació

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. Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR. _Nature Medicine_. 2015. Vol. 21, núm. 7, pàgs. 741-750. [consulta: 26 de gener de 2026]. ISSN: 1078-8956. [Disponible a: https://hdl.handle.net/2445/110925]

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