title: Conditional expression of fascin increases tumor progression in a mouse model of intestinal cancer.
abstract: While absent from normal epithelia, an actin bundling protein, fascin, becomes expressed in invasive carcinoma of different origins. It is highly enriched at the tumors' invasive front suggesting that it could play a role in cancer invasion. Multiple studies have shown that fascin, through its role in formation of cellular protrusions such as filopodia and invadopodia, enhances cancer cell migration and invasion in vitro. However, the role of fascin in vivo remains unknown. We have generated a compound transgenic mouse model that allows expression of fascin in the intestinal epithelium in the Apc-mutated background. Conditional expression of fascin led to decrease in mice survival and increase in tumor burden compared to control animals. Induction of fascin expression in adult tumor-bearing animals accelerated tumor progression and led to formation of invasive adenocarcinoma. Altogether, our study shows that fascin can promote tumor progression in vivo, but also unravels an unexpected role of fascin in tumor initiation.
authors.affiliation: Institut Curie, Research Center, 25 rue d'Ulm, 75248 Paris Cedex 05, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Schoumacher
authors.affiliation: Institut Curie, Research Center, 25 rue d'Ulm, 75248 Paris Cedex 05, France; UMR144/CNRS, 25 rue d'Ulm, 75248 Paris Cedex 05, France.
authors.forename: Fatima
authors.initials: F
authors.lastname: El-Marjou
authors.affiliation: Institut Curie, Hospital, 25 rue d'Ulm, 75248 Paris Cedex 05, France.
authors.forename: Marick
authors.initials: M
authors.lastname: Laé
authors.affiliation: Institut Curie, Research Center, 25 rue d'Ulm, 75248 Paris Cedex 05, France; UMR144/CNRS, 25 rue d'Ulm, 75248 Paris Cedex 05, France.
authors.forename: Nadège
authors.initials: N
authors.lastname: Kambou
authors.affiliation: Institut Curie, Research Center, 25 rue d'Ulm, 75248 Paris Cedex 05, France; UMR144/CNRS, 25 rue d'Ulm, 75248 Paris Cedex 05, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Louvard
authors.affiliation: Institut Curie, Research Center, 25 rue d'Ulm, 75248 Paris Cedex 05, France; UMR144/CNRS, 25 rue d'Ulm, 75248 Paris Cedex 05, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Robine
authors.affiliation: Institut Curie, Research Center, 25 rue d'Ulm, 75248 Paris Cedex 05, France; UMR144/CNRS, 25 rue d'Ulm, 75248 Paris Cedex 05, France. Electronic address: danijela.vignjevic@curie.fr.
authors.forename: Danijela Matic
authors.initials: DM
authors.lastname: Vignjevic
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation / Q000235:genetics; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis
chemical_list: D002352:Carrier Proteins; D008840:Microfilament Proteins; C020324:fascin
keywords: Colorectal cancer; Fascin; Invasion; Mouse model