Abstract
<div>Abstract<p>Most tumors are epithelial-derived, and although disruption of polarity and aberrant cellular junction formation is a poor prognosticator in human cancer, the role of polarity determinants in oncogenesis is poorly understood. Using <i>in vivo</i> selection, we identified a mammalian orthologue of the <i>Drosophila</i> polarity regulator <i>crumbs</i> as a gene whose loss of expression promotes tumor progression. Immortal baby mouse kidney epithelial cells selected <i>in vivo</i> to acquire tumorigenicity displayed dramatic repression of <i>crumbs3</i> (<i>crb3</i>) expression associated with disruption of tight junction formation, apicobasal polarity, and contact-inhibited growth. Restoration of <i>crb3</i> expression restored junctions, polarity, and contact inhibition while suppressing migration and metastasis. These findings suggest a role for mammalian polarity determinants in suppressing tumorigenesis that may be analogous to the well-studied polarity tumor suppressor mechanisms in <i>Drosophila</i>. [Cancer Res 2008;68(11):4105–15]</p></div>
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