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4. Data from Role of the Polarity Determinant Crumbs in Suppressing Mammalian Epithelial Tumor Progression

Author

Eileen White, Vassiliki Karantza-Wadsworth, Kurt Degenhardt, Chandreyee Mukherjee, Deidre Nelson, Robin Mathew, Ting Ting Tan, and Cristina M. Karp

Abstract

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]

Published
2023
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6. Role of the Polarity Determinant Crumbs in Suppressing Mammalian Epithelial Tumor Progression

Author

Kurt Degenhardt, Deidre Nelson, Vassiliki Karantza-Wadsworth, Robin Mathew, Eileen White, Cristina M. Karp, Chandreyee Mukherjee, and Ting Ting Tan

Subjects
Cancer Research, Cell division, Polarity (physics), Gene Expression, Biology, medicine.disease_cause, Article, law.invention, Cell Line, Tight Junctions, Mice, law, medicine, Animals, Genes, Tumor Suppressor, Neoplasms, Glandular and Epithelial, Epithelial polarity, Oligonucleotide Array Sequence Analysis, Membrane Glycoproteins, Tight junction, Contact inhibition, Membrane Proteins, Immunohistochemistry, Cell biology, Oncology, Tumor progression, Suppressor, Carcinogenesis, Cell Division
Abstract

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]

Published
2008

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