Loss of cell polarity proteins such as Scribble induces neoplasia in Drosophila 
by promoting uncontrolled proliferation. In mammals, the role that polarity 
proteins play during tumorigenesis is not well understood. Here, we demonstrate 
that depletion of Scribble in mammary epithelia disrupts cell polarity, blocks 
three-dimensional morphogenesis, inhibits apoptosis, and induces dysplasia in 
vivo that progress to tumors after long latency. Loss of Scribble cooperates 
with oncogenes such as c-myc to transform epithelial cells and induce tumors in 
vivo by blocking activation of an apoptosis pathway. Like depletion, 
mislocalization of Scribble from cell-cell junction was sufficient to promote 
cell transformation. Interestingly, spontaneous mammary tumors in mice and 
humans possess both downregulated and mislocalized Scribble. Thus, we 
demonstrate that scribble inhibits breast cancer formation and that deregulation 
of polarity pathways promotes dysplastic and neoplastic growth in mammals by 
disrupting morphogenesis and inhibiting cell death.