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

Eva Pérez-Guijarro, Panagiotis Karras, Metehan Cifdaloz, Raúl Martínez-Herranz, Estela Cañón, Osvaldo Graña, Celia Horcajada-Reales, Direna Alonso-Curbelo, Tonantzin G. Calvo, Gonzalo Gómez-López, Nicolas Bellora, Erica Riveiro-Falkenbach, Pablo L. Ortiz-Romero, José L. Rodríguez-Peralto, Lorena Maestre, Giovanna Roncador, Juan C. de Agustín Asensio, Colin R. Goding, Eduardo Eyras, Diego Megías, Raúl Méndez and María S. Soengas ()
Additional contact information
Eva Pérez-Guijarro: Melanoma Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO)
Panagiotis Karras: Melanoma Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO)
Metehan Cifdaloz: Melanoma Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO)
Raúl Martínez-Herranz: Melanoma Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO)
Estela Cañón: Melanoma Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO)
Osvaldo Graña: Bioinformatics Unit (CNIO)
Celia Horcajada-Reales: Hospital Gregorio Marañón
Direna Alonso-Curbelo: Melanoma Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO)
Tonantzin G. Calvo: Melanoma Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO)
Gonzalo Gómez-López: Bioinformatics Unit (CNIO)
Nicolas Bellora: Universidad Pompeu Fabra
Erica Riveiro-Falkenbach: Instituto de Investigación i+12, Hospital 12 de Octubre, Medical School, Universidad Complutense
Pablo L. Ortiz-Romero: Instituto de Investigación i+12, Hospital 12 de Octubre, Medical School, Universidad Complutense
José L. Rodríguez-Peralto: Instituto de Investigación i+12, Hospital 12 de Octubre, Medical School, Universidad Complutense
Lorena Maestre: Monoclonal Antibodies Unit, Biotechnology Programme (CNIO)
Giovanna Roncador: Monoclonal Antibodies Unit, Biotechnology Programme (CNIO)
Juan C. de Agustín Asensio: Hospital Gregorio Marañón
Colin R. Goding: Institute for Cancer Research, University of Oxford
Eduardo Eyras: Universidad Pompeu Fabra
Diego Megías: Confocal Microscopy Unit, (CNIO)
Raúl Méndez: Institució Catalana de Recerca i Estudis Avançats (ICREA)
María S. Soengas: Melanoma Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO)

Nature Communications, 2016, vol. 7, issue 1, 1-17

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms13418

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