The Fragile X Protein binds mRNAs involved in cancer progression and modulates metastasis formation

EMBO Molecular Medicine

Rossella Lucá¹³  Michele Averna¹³  Francesca Zalfa¹  Manuela Vecchi¹⁰  Fabrizio Bianchi³  Giorgio La Fata¹³  Franca Del Nonno¹⁴  Roberta Nardacci¹⁴  Marco Bianchi¹⁰  Paolo Nuciforo⁷  Sebastian Munck¹³  Paola Parrella⁴  Rute Moura¹³  Emanuela Signori⁶  Robert Alston¹²  Anna Kuchnio^5,13  Maria Giulia Farace^8,13  Vito Michele Fazio⁴  Mauro Piacentini¹⁴  Bart De Strooper¹³  Tilmann Achsel¹³  Giovanni Neri^2,13  Patrick Neven^11,13  D. Gareth Evans¹²  Peter Carmeliet^5,13  Massimiliano Mazzone^9,13 

[1] CIR Department, Faculty of Medicine, University “Campus Bio-Medico”, Rome, Italy;Institute of Medical Genetics, Catholic University, Rome, Italy;Molecular Medicine Program, Department of Experimental Oncology, European Institute of Oncology, Milan, Italy;Laboratory of Oncology, IRCCS H. “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, Italy;Laboratory of Angiogenesis and Neurovascular Link, Vesalius Research Center, VIB, Leuven, Belgium;Institute of Translational Pharmacology, CNR, Rome, Italy;Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Barcelona, Spain;Department of Biomedicine and Prevention, University “Tor Vergata”, Rome, Italy;Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB, Leuven, Belgium;IFOM, Fondazione Istituto FIRC di Oncologia Moleculare, Milan, Italy;Department of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven, Belgium;Cancer Research UK Paediatric and Familial Cancer Research Group, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK;VIB Center for the Biology of Disease, Leuven, Belgium;National Institute for Infectious Diseases, IRCCS ‘Lazzaro Spallanzani’, Rome, Italy

关键词: cell invasion;    EMT;    FMRP;    mRNA metabolism;    TNBC;   

DOI  :  10.1002/emmm.201302847

来源: Wiley

【 摘 要 】

Abstract

The role of the fragile X mental retardation protein (FMRP) is well established in brain, where its absence leads to the fragile X syndrome (FXS). FMRP is almost ubiquitously expressed, suggesting that, in addition to its effects in brain, it may have fundamental roles in other organs. There is evidence that FMRP expression can be linked to cancer. FMR1 mRNA, encoding FMRP, is overexpressed in hepatocellular carcinoma cells. A decreased risk of cancer has been reported in patients with FXS while a patient-case with FXS showed an unusual decrease of tumour brain invasiveness. However, a role for FMRP in regulating cancer biology, if any, remains unknown. We show here that FMRP and FMR1 mRNA levels correlate with prognostic indicators of aggressive breast cancer, lung metastases probability and triple negative breast cancer (TNBC). We establish that FMRP overexpression in murine breast primary tumours enhances lung metastasis while its reduction has the opposite effect regulating cell spreading and invasion. FMRP binds mRNAs involved in epithelial mesenchymal transition (EMT) and invasion including E-cadherin and Vimentin mRNAs, hallmarks of EMT and cancer progression.

【 授权许可】

CC BY   
Copyright © 2013 EMBO Molecular Medicine

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.