The fragile X mental retardation protein regulates tumor invasiveness-related pathways in melanoma cells

Francesca Zalfa, Vincenzo Panasiti, Simone Carotti, Maria Zingariello, Giuseppe Perrone, Laura Sancillo, Laura Pacini, Flavie Luciani, Vincenzo Roberti, Silvia D'Amico, Rosa Coppola, Simona Osella Abate, Rosa Alba Rana, Anastasia De Luca, Mark Fiers, Valentina Melocchi, Fabrizio Bianchi, Maria Giulia Farace, Tilmann Achsel, Jean Christophe MarineSergio Morini, Claudia Bagni

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Abstract

The fragile X mental retardation protein (FMRP) is lacking or mutated in patients with the fragile X syndrome (FXS), the most frequent form of inherited intellectual disability. FMRP affects metastasis formation in a mouse model for breast cancer. Here we show that FMRP is overexpressed in human melanoma with high Breslow thickness and high Clark level. Furthermore, metaanalysis of the TCGA melanoma data revealed that high levels of FMRP expression correlate significantly with metastatic tumor tissues, risk of relapsing and disease-free survival. Reduction of FMRP in metastatic melanoma cell lines impinges on cell migration, invasion and adhesion. Next-generation sequencing in human melanoma cells revealed that FMRP regulates a large number of mRNAs involved in relevant processes of melanoma progression. Our findings suggest an association between FMRP levels and the invasive phenotype in melanoma and might open new avenues towards the discovery of novel therapeutic targets.

Original languageEnglish
Article numbere3169
JournalCell Death and Disease
Volume8
Issue number11
DOIs
Publication statusPublished - Nov 1 2017

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ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Cite this

Zalfa, F., Panasiti, V., Carotti, S., Zingariello, M., Perrone, G., Sancillo, L., Pacini, L., Luciani, F., Roberti, V., D'Amico, S., Coppola, R., Abate, S. O., Rana, R. A., De Luca, A., Fiers, M., Melocchi, V., Bianchi, F., Farace, M. G., Achsel, T., ... Bagni, C. (2017). The fragile X mental retardation protein regulates tumor invasiveness-related pathways in melanoma cells. Cell Death and Disease, 8(11), [e3169]. https://doi.org/10.1038/cddis.2017.521