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.