title: The RNA-binding protein ESRP1 promotes human colorectal cancer progression.
abstract: 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.
authors.affiliation: Institute of Biostructure and Bioimaging, CNR, Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy.|Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy.
authors.forename: Sharmila
authors.initials: S
authors.lastname: Fagoonee
authors.affiliation: Candiolo Cancer Institute-IRCCS, University of Turin, Italy.|present address: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Picco
authors.affiliation: Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Orso
authors.affiliation: S.C. Gastroenterologia U, Endoscopia San Giovanni A.S., Azienda Città' della Salute e della Scienza di Torino, Turin, Italy.
authors.forename: Arrigo
authors.initials: A
authors.lastname: Arrigoni
authors.affiliation: Institute of Biostructure and Bioimaging, CNR, Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy.|Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy.
authors.forename: Dario L
authors.initials: DL
authors.lastname: Longo
authors.affiliation: EuroClone S.p.A Research Laboratory, Molecular Biotechnology Centre, University of Turin, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Forni
authors.affiliation: Center for Experimental Research and Medical Studies, University of Turin, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Scarfò
authors.affiliation: Department of Medical Sciences, University of Turin, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: Cassenti
authors.affiliation: Center for Experimental Research and Medical Studies, University of Turin, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Piva
authors.affiliation: Department of Medical Sciences, University of Turin, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Cassoni
authors.affiliation: Institute of Biostructure and Bioimaging, CNR, Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy.|Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Silengo
authors.affiliation: Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Tolosano
authors.affiliation: Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
authors.affiliation: Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Taverna
authors.affiliation: Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy.|Cancer Research Institute, BIDMC, Harvard Medical School, Boston, USA.
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Pandolfi
authors.affiliation: Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Brancaccio
authors.affiliation: Candiolo Cancer Institute-IRCCS, University of Turin, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Medico
authors.affiliation: Institute of Biostructure and Bioimaging, CNR, Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy.|Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Altruda
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D061206:Neoplasm Micrometastasis; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden
chemical_list: C539364:ESRP1 protein, human; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016601:RNA-Binding Proteins; D000071250:Snail Family Transcription Factors; D058539:Phosphatidylinositol 3-Kinase; C496348:FGFR1 protein, human; C496353:FGFR2 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051057:Proto-Oncogene Proteins c-akt
keywords: ESRP1; RNA binding protein; human colorectal cancer; proto-oncogene