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Nat Commun. 2016 Nov 18;7:13418. doi: 10.1038/ncomms13418.

Lineage-specific roles of the cytoplasmic polyadenylation factor CPEB4 in the regulation of melanoma drivers.

Author information

1
Melanoma Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
2
Bioinformatics Unit (CNIO), Madrid 28029, Spain.
3
Department of Dermatology, Hospital Gregorio Marañón, Madrid 28003, Spain.
4
Department of Experimental and Health Sciences, Universidad Pompeu Fabra, Barcelona 08002, Spain.
5
Instituto de Investigación i+12, Hospital 12 de Octubre, Medical School, Universidad Complutense, Madrid 28041, Spain.
6
Monoclonal Antibodies Unit, Biotechnology Programme (CNIO), Madrid 28029, Spain.
7
Department of Pediatric Surgery, Hospital Gregorio Marañón, Madrid 28003, Spain.
8
Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, Spain.
9
Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona 08010, Spain.
10
Confocal Microscopy Unit, (CNIO) Madrid 28029, Spain.
11
Translational Control of Cell Cycle and Differentiation Group, Molecular Medicine Department, Institute for Research in Biomedicine (IRB), The Barcelona Institute of Science and Technology, Barcelona 08028, Spain.

Abstract

Nuclear 3'-end-polyadenylation is essential for the transport, stability and translation of virtually all eukaryotic mRNAs. Poly(A) tail extension can also occur in the cytoplasm, but the transcripts involved are incompletely understood, particularly in cancer. Here we identify a lineage-specific requirement of the cytoplasmic polyadenylation binding protein 4 (CPEB4) in malignant melanoma. CPEB4 is upregulated early in melanoma progression, as defined by computational and histological analyses. Melanoma cells are distinct from other tumour cell types in their dependency on CPEB4, not only to prevent mitotic aberrations, but to progress through G1/S cell cycle checkpoints. RNA immunoprecipitation, sequencing of bound transcripts and poly(A) length tests link the melanoma-specific functions of CPEB4 to signalling hubs specifically enriched in this disease. Essential in these CPEB4-controlled networks are the melanoma drivers MITF and RAB7A, a feature validated in clinical biopsies. These results provide new mechanistic links between cytoplasmic polyadenylation and lineage specification in melanoma.

PMID:
27857118
PMCID:
PMC5120223
DOI:
10.1038/ncomms13418
[Indexed for MEDLINE]
Free PMC Article

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