title: Aberrant overexpression of the cell polarity module scribble in human cancer.
abstract: Human Scribble (Scrib) is an evolutionary-conserved cell polarity protein, but its potential role in human cancer is controversial. Herein, we show that Scrib is nearly universally overexpressed in cultured tumor cell lines and genetically disparate cancer patient series compared with matched normal tissues in vivo. Instead of a membrane association seen in normal epithelia, tumor-associated Scrib is mislocalized and found predominantly in the cytosol. Small-interfering RNA silencing of Scrib in model lung adenocarcinoma A549 cells inhibited cell migration in wound-healing assays, suppressed tumor cell invasion across Matrigel-coated inserts, and down-regulated the expression of cell motility markers and mediators of epithelial-mesenchymal transition. These data uncover a previously unrecognized exploitation of Scrib for aberrant tumor cell motility and invasion, thus potentially contributing to disease progression in humans.
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Vaira
authors.forename: Alice
authors.initials: A
authors.lastname: Faversani
authors.forename: Takehiko
authors.initials: T
authors.lastname: Dohi
authors.forename: Marco
authors.initials: M
authors.lastname: Maggioni
authors.forename: Mario
authors.initials: M
authors.lastname: Nosotti
authors.forename: Delfina
authors.initials: D
authors.lastname: Tosi
authors.forename: Dario C
authors.initials: DC
authors.lastname: Altieri
authors.forename: Silvano
authors.initials: S
authors.lastname: Bosari
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D016764:Cell Polarity / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D046888:Tissue Array Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; C480591:SCRIB protein, human; D025521:Tumor Suppressor Proteins