Aberrant overexpression of the cell polarity module Scribble in human cancer

Valentina Vaira, Alice Faversani, Takehiko Dohi, Marco Maggioni, Mario Nosotti, Delfina Tosi, Dario C. Altieri, Silvano Bosari

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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 Matrigelcoated 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.

Original languageEnglish (US)
Pages (from-to)2478-2483
Number of pages6
JournalAmerican Journal of Pathology
Volume178
Issue number6
DOIs
StatePublished - Jun 2011

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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    Vaira, V., Faversani, A., Dohi, T., Maggioni, M., Nosotti, M., Tosi, D., Altieri, D. C., & Bosari, S. (2011). Aberrant overexpression of the cell polarity module Scribble in human cancer. American Journal of Pathology, 178(6), 2478-2483. https://doi.org/10.1016/j.ajpath.2011.02.028