Published in

Nature Research, Nature Medicine, 7(21), p. 741-750, 2015

DOI: 10.1038/nm.3863

Links

Tools

Export citation

Search in Google Scholar

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

Journal article published in 2015 by Joost van den Oord, Ferreira HJ Lopez-Serra P Carmona FJ Martínez-Cardús A Girotti MR Villanueva A Guil S Moutinho C Liz J Portela A Heyn H Moran S Vidal A Martinez-Iniesta M Manzano JL Fernandez-Figueras MT Elez E Muñoz-Couselo E Botella-Estrada R Berrocal A Pontén F Oord JV Vizoso M., Miguel Vizoso ORCID, Humberto J. Ferreira, Paula Lopez-Serra, F. Javier Carmona, Anna Martínez-Cardús, Maria Romina Girotti, Alberto Villanueva, Sonia Guil ORCID, Catia Moutinho, F. Javier Carmona, Julia Liz, Anna Portela, Holger Heyn and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

Full text: Download

Green circle
Preprint: archiving allowed
Upload
Orange circle
Postprint: archiving restricted
Upload
Red circle
Published version: archiving forbidden
Policy details
Data provided by SHERPA/RoMEO

Abstract

Metastasis 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.