The RNA-binding protein ESRP1 promotes human colorectal cancer progression
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Sharmila Fagoonee1,2, Gabriele Picco3,9, Francesca Orso2, Arrigo Arrigoni4, Dario L. Longo1,2, Marco Forni5, Irene Scarfò6, Adele Cassenti7, Roberto Piva6, Paola Cassoni7, Lorenzo Silengo1,2, Emanuela Tolosano2, Silvio Aime2, Daniela Taverna2, Pier Paolo Pandolfi2,8, Mara Brancaccio2, Enzo Medico3, Fiorella Altruda1,2
1Institute of Biostructure and Bioimaging, CNR, Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy
2Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy
3Candiolo Cancer Institute-IRCCS, University of Turin, Italy
4S.C. Gastroenterologia U, Endoscopia San Giovanni A.S., Azienda Città' della Salute e della Scienza di Torino, Turin, Italy
5EuroClone S.p.A Research Laboratory, Molecular Biotechnology Centre, University of Turin, Italy
6Center for Experimental Research and Medical Studies, University of Turin, Italy
7Department of Medical Sciences, University of Turin, Italy
8Cancer Research Institute, BIDMC, Harvard Medical School, Boston, USA
9present address: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK
Sharmila Fagoonee, email: [email protected]
Fiorella Altruda, email: [email protected]
Keywords: ESRP1, RNA binding protein, proto-oncogene, human colorectal cancer
Received: June 08, 2016 Accepted: December 01, 2016 Published: December 28, 2016
Epithelial splicing regulatory protein 1 (ESRP1) is an epithelial cell-specific RNA binding protein that controls several key cellular processes, like alternative splicing and translation. Previous studies have demonstrated a tumor suppressor role for this protein. Recently, however, a pro-metastatic function of ESRP1 has been reported. We thus aimed at clarifying the role of ESRP1 in Colorectal Cancer (CRC) by performing loss- and gain-of-function studies, and evaluating tumorigenesis and malignancy with in vitro and in vivo approaches. We found that ESRP1 plays a role in anchorage-independent growth of CRC cells. ESRP1-overexpressing cells grown in suspension showed enhanced fibroblast growth factor receptor (FGFR1/2) signalling, Akt activation, and Snail upregulation. Moreover, ESRP1 promoted the ability of CRC cells to generate macrometastases in mice livers. High ESRP1 expression may thus stimulate growth of cancer epithelial cells and promote colorectal cancer progression. Our findings provide mechanistic insights into a previously unreported, pro-oncogenic role for ESRP1 in CRC, and suggest that fine-tuning the level of this RNA-binding protein could be relevant in modulating tumor growth in a subset of CRC patients.
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