Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR.
Girotti, Maria Romina
Van Den Oord, J
Lorigan, Paul C
AffiliationCancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, L'Hospitalet, Barcelona,
MetadataShow full item record
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.
CitationEpigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR. 2015: Nat Med
- TBC1D16 is a Rab4A GTPase activating protein that regulates receptor recycling and EGF receptor signaling.
- Authors: Goueli BS, Powell MB, Finger EC, Pfeffer SR
- Issue date: 2012 Sep 25
- Targeting melanoma: unusual epigenetics reveals the dynamic rewiring of metastatic cells.
- Authors: Vizoso M, Esteller M
- Issue date: 2015 Oct
- Characterisation of DNA methylation changes in EBF3 and TBC1D16 associated with tumour progression and metastasis in multiple cancer types.
- Authors: Rodger EJ, Chatterjee A, Stockwell PA, Eccles MR
- Issue date: 2019 Aug 5
- Epigenetic silencing of TET2 and TET3 induces an EMT-like process in melanoma.
- Authors: Gong F, Guo Y, Niu Y, Jin J, Zhang X, Shi X, Zhang L, Li R, Chen L, Ma RZ
- Issue date: 2017 Jan 3
- Reversible and adaptive resistance to BRAF(V600E) inhibition in melanoma.
- Authors: Sun C, Wang L, Huang S, Heynen GJ, Prahallad A, Robert C, Haanen J, Blank C, Wesseling J, Willems SM, Zecchin D, Hobor S, Bajpe PK, Lieftink C, Mateus C, Vagner S, Grernrum W, Hofland I, Schlicker A, Wessels LF, Beijersbergen RL, Bardelli A, Di Nicolantonio F, Eggermont AM, Bernards R
- Issue date: 2014 Apr 3