Role of the polarity determinant crumbs in suppressing mammalian epithelial tumor progression

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

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4105-4115
Number of pages11
JournalCancer Research
Volume68
Issue number11
DOIs
StatePublished - Jun 1 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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