title: NPM1 silencing reduces tumour growth and MAPK signalling in prostate cancer cells.
abstract: The chaperone nucleophosmin (NPM1) is over-expressed in the epithelial compartment of prostate tumours compared to adjacent healthy epithelium and may represent one of the key actors that support the neoplastic phenotype of prostate adenocarcinoma cells. Yet, the mechanisms that underlie NPM1 mediated phenotype remain elusive in the prostate. To better understand NPM1 functions in prostate cancer cells, we sought to characterize its impact on prostate cancer cells behaviour and decipher the mechanisms by which it may act. Here we show that NPM1 favors prostate tumour cell migration, invasion and colony forming. Furthermore, knockdown of NPM1 leads to a decrease in the growth of LNCaP-derived tumours grafted in Nude mice in vivo. Such oncogenic-like properties are found in conjunction with a positive regulation of NPM1 on the ERK1/2 (Extracellular signal-Regulated Kinases 1/2) kinase phosphorylation in response to EGF (Epidermal Growth Factor) stimulus, which is critical for prostate cancer progression following the setting of an autonomous production of the growth factor. NPM1 could then be a target to switch off specifically ERK1/2 pathway activation in order to decrease or inhibit cancer cell growth and migration.
authors.affiliation: Clermont Université, Université Blaise Pascal, GReD, Clermont-Ferrand, France; CNRS, UMR 6293, GReD, Clermont-Ferrand, France; Inserm, UMR 1103, GReD - Genetics, Reproduction and Development, Clermont-Ferrand, France; CRNH, Centre de Recherche en Nutrition Humaine, Clermont-Ferrand.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Loubeau
authors.affiliation: Clermont Université, Université Blaise Pascal, GReD, Clermont-Ferrand, France; CNRS, UMR 6293, GReD, Clermont-Ferrand, France; Inserm, UMR 1103, GReD - Genetics, Reproduction and Development, Clermont-Ferrand, France; CRNH, Centre de Recherche en Nutrition Humaine, Clermont-Ferrand.
authors.forename: Rafik
authors.initials: R
authors.lastname: Boudra
authors.affiliation: Clermont Université, Université Blaise Pascal, GReD, Clermont-Ferrand, France; CNRS, UMR 6293, GReD, Clermont-Ferrand, France; Inserm, UMR 1103, GReD - Genetics, Reproduction and Development, Clermont-Ferrand, France; CRNH, Centre de Recherche en Nutrition Humaine, Clermont-Ferrand.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Maquaire
authors.affiliation: Clermont Université, Université Blaise Pascal, GReD, Clermont-Ferrand, France; CNRS, UMR 6293, GReD, Clermont-Ferrand, France; Inserm, UMR 1103, GReD - Genetics, Reproduction and Development, Clermont-Ferrand, France; CRNH, Centre de Recherche en Nutrition Humaine, Clermont-Ferrand.
authors.forename: Corinne
authors.initials: C
authors.lastname: Lours-Calet
authors.affiliation: Clermont Université, Université Blaise Pascal, GReD, Clermont-Ferrand, France; CNRS, UMR 6293, GReD, Clermont-Ferrand, France; Inserm, UMR 1103, GReD - Genetics, Reproduction and Development, Clermont-Ferrand, France; CRNH, Centre de Recherche en Nutrition Humaine, Clermont-Ferrand.
authors.forename: Claude
authors.initials: C
authors.lastname: Beaudoin
authors.affiliation: Clermont Université, Université d'Auvergne, EA 7283 CREaT -Cancer Resistance Exploring and Targeting, Clermont-Ferrand, France; Centre Jean Perrin, Clermont-Ferrand, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Verrelle
authors.affiliation: Clermont Université, Université Blaise Pascal, GReD, Clermont-Ferrand, France; CNRS, UMR 6293, GReD, Clermont-Ferrand, France; Inserm, UMR 1103, GReD - Genetics, Reproduction and Development, Clermont-Ferrand, France; CRNH, Centre de Recherche en Nutrition Humaine, Clermont-Ferrand.
authors.forename: Laurent
authors.initials: L
authors.lastname: Morel
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000090243:Nucleophosmin; D011471:Prostatic Neoplasms / Q000378:metabolism*
chemical_list: C000716967:NPM1 protein, human; C000715570:Npm1 protein, mouse; D009687:Nuclear Proteins; D000090243:Nucleophosmin