Role of the polarity determinant crumbs in suppressing mammalian epithelial tumor progression.
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.
Karp
Cristina M
CM
Department of Molecular Biology and Biochemistry, Center for Advanced Biotechnology and Medicine, Rutgers University, NJ 08854, USA.
Tan
Ting Ting
TT
Mathew
Robin
R
Nelson
Deidre
D
Mukherjee
Chandreyee
C
Degenhardt
Kurt
K
Karantza-Wadsworth
Vassiliki
V
White
Eileen
E
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D020411:Oligonucleotide Array Sequence Analysis; D019108:Tight Junctions
C530695:Crb3 protein, mouse; D008562:Membrane Glycoproteins; D008565:Membrane Proteins