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Role of the Polarity Determinant Crumbs in Suppressing Mammalian Epithelial Tumor Progression

¹ Department of Molecular Biology and Biochemistry, Center for Advanced Biotechnology and Medicine, Rutgers University; ² Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey and ³ The Cancer Institute of New Jersey, New Brunswick, New Jersey

Requests for reprints: Eileen White, Center for Advanced Biotechnology and Medicine, 679 Hoes Lane, Piscataway, NJ 08854. Phone: 732-235-5329; Fax: 732-235-5795; E-mail: ewhite{at}cabm.rutgers.edu.

Key Words: Crumbs • crb3 • tight junctions • polarity • metastasis • cancer

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 in vivo selection, we identified a mammalian orthologue of the Drosophila polarity regulator crumbs as a gene whose loss of expression promotes tumor progression. Immortal baby mouse kidney epithelial cells selected in vivo to acquire tumorigenicity displayed dramatic repression of crumbs3 (crb3) expression associated with disruption of tight junction formation, apicobasal polarity, and contact-inhibited growth. Restoration of crb3 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 Drosophila. [Cancer Res 2008;68(11):4105–15]

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