Abstract：
: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.
journal_name
Celljournal_title
Cellauthors
Zhan L,Rosenberg A,Bergami KC,Yu M,Xuan Z,Jaffe AB,Allred C,Muthuswamy SKdoi
10.1016/j.cell.2008.09.045subject
Has Abstractpub_date
2008-11-28 00:00:00pages
865-78issue
5eissn
0092-8674issn
1097-4172pii
S0092-8674(08)01238-5journal_volume
135pub_type
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