title: Fibulin-5 downregulates Ki-67 and inhibits proliferation and invasion of breast cancer cells.
abstract: Fibulins not only function as molecular bridges within the cellular microenvironment but also influence cell behavior. Thus, fibulins may contribute to create a permissive microenvironment for tumor growth but can also stimulate different mechanisms that may impede tumor progression. This is the case with Fibulin-5, which has been shown to display both tumor-promoting and tumor-protective functions by mechanisms that are not totally defined. We show new evidence on the tumor-protective functions displayed by Fibulin-5 in MCF-7, T47D and MDA-MB-231 breast cancer cells including the inhibition of invasion and proliferation capacity and hampering the ability to form mammospheres. Reduction in the level of phosphorylation of Ser residues involved in the nuclear translocation of β-catenin may underlie these antitumor effects. We also found that Fibulin-5 reduces the level of expression of Ki-67, a nuclear protein associated with cell proliferation. Moreover, reduction in Fibulin-5 expression corresponds to an increase of Ki-67 detection in breast tissue samples. Overall, our data provide new insights into the influence of Fibulin-5 to modify breast cancer cell behavior and contribute to better understand the connections between fibulins and cancer.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Oviedo, Oviedo, Spain.
authors.forename: Yamina
authors.initials: Y
authors.lastname: Mohamedi
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Oviedo, Oviedo, Spain.
authors.forename: Tania
authors.initials: T
authors.lastname: Fontanil
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Oviedo, Oviedo, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Solares
authors.affiliation: Department of Morphology and Cellular Biology, Faculty of Medicine, University of Oviedo, Oviedo, Spain.
authors.forename: Olivia
authors.initials: O
authors.lastname: Garcia-Suárez
authors.affiliation: Department of Morphology and Cellular Biology, Faculty of Medicine, University of Oviedo, Oviedo, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: García-Piqueras
authors.affiliation: Department of Morphology and Cellular Biology, Faculty of Medicine, University of Oviedo, Oviedo, Spain.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Vega
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Oviedo, Oviedo, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Cal
authors.affiliation: Department of Functional Biology-Physiology, Faculty of Medicine, University of Oviedo, Oviedo, Spain.
authors.forename: Alvaro J
authors.initials: AJ
authors.lastname: Obaya
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis* / Q000235:genetics; D061986:MCF-7 Cells; D009361:Neoplasm Invasiveness / Q000235:genetics; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: D016326:Extracellular Matrix Proteins; C492373:FBLN5 protein, human; D019394:Ki-67 Antigen